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The immunobiology of myiasis infections--whatever happened to vaccination?

- Sandeman, Mark, Bowles, Vern, Colwell, Doug

  • Authors: Sandeman, Mark , Bowles, Vern , Colwell, Doug
  • Date: 2014
  • Type: Text , Journal article
  • Relation: Parasite immunology Vol. 36, no. 11 (2014), p. 605-615
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  • Description: The current state of myiasis vaccine technologies are reviewed mainly in the primary research genera of Lucilia and Hypoderma. The importance of myiasis flies as primary causes of morbidity and mortality in agricultural species and man has not diminished despite the existence of good control strategies. However, the development of vaccines against myiasis infections has been relatively quiescent for more than 10 years despite the rapid development of genomic and proteomic analysis and of skills in data interpretation. The value of vaccine research in an era of chemical primacy is analysed. In fact, recent findings of drug resistance and the impact of animal welfare concerns should mean a renewed interest in alternative controls. The reasons that this has not been true to date are explored and new possibilities discussed.

Immune mechanisms of resistance to gastrointestinal nematode infections in sheep

- Hein, W., Pernthaner, A., Piedrafita, David, Meeusen, Els

  • Authors: Hein, W. , Pernthaner, A. , Piedrafita, David , Meeusen, Els
  • Date: 2010
  • Type: Text , Journal article
  • Relation: Parasite Immunology Vol. 32, no. 8 (2010), p. 541-548
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  • Description: Infections with gastrointestinal nematode parasites are a major problem for the sheep industry in Australia and New Zealand and have been the subject of intensive research to define mechanisms of resistance. The ability to take continuous biopsy samples of infected organs and cannulate both afferent and efferent lymphatics of draining lymph nodes has been particularly useful in illuminating the kinetics of immune responses at the site of infection. Distinct localized immune responses were shown to occur within and between sheep breeds at different sensitization regimes, as well as at different developmental stages of the parasite within the host. Using localized antibodies derived from mucus and lymph nodes, two major antigens have been identified on the infective L3 stage, which may be responsible for inducing protection and have potential as vaccine targets. Recent advances in sheep genomics also offer the potential of gaining further insight into the underlying genetics of resistance to nematode infections.

Evaluation of colorimetric detection methods for Shigella, Salmonella, and Vibrio cholerae by loop-mediated isothermal amplification

- Soli, Kevin, Kas, Monalisa, Maure, Tobias, Umezaki, Masahiro, Morita, Ayako, Siba, Peter, Greenhill, Andrew, Horwood, Paul

Improving animal and human health through understanding liver fluke immunology

- Piedrafita, David, Spithill, Terry, Smith, Rebecca, Raadsma, Herman

  • Authors: Piedrafita, David , Spithill, Terry , Smith, Rebecca , Raadsma, Herman
  • Date: 2010
  • Type: Text , Journal article
  • Relation: Parasite Immunology Vol. 32, no. 8 (2010), p. 572-581
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  • Description: Sheep, goats and cattle represent the most numerous and economically important agricultural species worldwide used as sources for milk, fibre and red meat. In addition, in the developing world, these species often represent the sole asset base for small-holder livestock farmers and cattle/buffaloes often provide the majority of draught power for crop production. Production losses caused by helminth diseases of these animals are a major factor in extending the cycle of poverty in developing countries and a major food security issue for developed economies. Fasciola spp. are one of the most important zoonotic diseases with a global economic impact in livestock production systems and a poorly defined but direct effect on human health. Improvements in human and animal health will require a concerted research effort into the development of new accurate and simple diagnostic tests and increased vaccine and drug development against Fasciola infections. Here, the use of definitive natural host breeds with contrasting resistance to Fasciola infections is discussed as a resource to contrast parasite–host interactions and identify parasite immune evasion strategies. Such studies are likely to boost the discovery of new vaccine, drug and diagnostic candidates and provide the foundation for future genetic selection of resistant animals.

Plasmids imparting sulfonamide resistance in Escherichia coli: Implications for persistence

- Bean, David, Livermore, David, Hall, Lucinda

  • Authors: Bean, David , Livermore, David , Hall, Lucinda
  • Date: 2009
  • Type: Text , Journal article
  • Relation: Antimicrobial Agents and Chemotherapy Vol. 53, no. 3 (2009), p. 1088-1093
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  • Description: Sulfonamide resistance remains prevalent among clinical isolates of Escherichia coli in the United Kingdom, despite a dramatic (>97%) national decline in the rate of prescription of sulfonamides in the 1990s. To investigate potential mechanisms accounting for this persistence, we characterized plasmids carrying sul2, the most prevalent determinant of sulfonamide resistance. Among 33 conjugative and 5 nonconjugative plasmids carrying sul2, resistance to other antimicrobial agents was common, but the spectrum of resistance profiles was diverse: 82%, 74%, and 45% carried resistance to ampicillin, streptomycin, and trimethoprim, respectively. Resistance to mercury was carried by 33% of the plasmids, but none conferred significant resistance to silver or to any of three disinfectants tested. The potential virulence genes iutA (aerobactin system) and traT (serum survival) were carried by 21% and 36% of the plasmids, respectively. The 33 conjugative plasmids belonged to five different incompatibility groups, FIB, B/O, I1, K/B, and P (42%, 33%, 9%, 3% and 3%, respectively), with 3 plasmids being unassigned, and to 19 similarity groups on the basis of their restriction profiles. The sequences flanking sul2 were diverse and suggested more than one mechanism of genetic mobility. The five nonconjugative plasmids were all related to p9123 (pBP1), which was previously found to confer a fitness advantage on its host. We propose that the persistence of sul2, despite the reduced rate of prescription of sulfonamides, is due to a combination of coselection by antibiotics still in common use, a lack of a selective disadvantage in sul2 carriage, and the genetic mobility of sul2. Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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Paradoxical effect of 1-(1-naphthylmethyl)-piperazine on resistance to tetracyclines in multidrug-resistant Acinetobacter baumannii

- Bean, David, Wareham, David

  • Authors: Bean, David , Wareham, David
  • Date: 2009
  • Type: Text , Journal article
  • Relation: Journal of Antimicrobial Chemotherapy Vol. 63, no. 2 (2009), p. 349-352
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  • Description: Objectives The efflux inhibitor 1-(1-naphthylmethyl)-piperazine (NMP) has been demonstrated to reverse multidrug resistance in Acinetobacter baumannii. We investigated the interaction of NMP with tigecycline and three other tetracyclines on clinical isolates of A. baumannii. Methods One hundred and four clinical isolates of Acinetobacter were tested for susceptibility to tigecycline, minocycline, doxycycline and tetracycline by disc diffusion, and tigecycline MICs were determined by Etest, both in the presence and absence of NMP. Tigecycline MICs and zones of inhibition were interpreted using the BSAC guidelines. An OXA carbapenemase multiplex PCR was also performed on each isolate. Results Mean zones of inhibition for tetracycline, doxycycline and minocycline increased by 11.3%, 22.9% and 11.2%, respectively, in the presence of NMP. In contrast, tigecycline susceptibility was decreased in the presence of NMP, with mean zones of inhibition decreasing by 8.4%. Based on PCR results, all but six isolates belonged to the OXA-23 clone 1. Conclusions Susceptibility to tigecycline of the A. baumannii OXA-23 clone 1 prevalent in the UK is reduced (∼2-fold) by the presence of the efflux inhibitor NMP. NMP does not have the same effect on susceptibility to other tetracyclines.
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Resistance to liver fluke infection in the natural sheep host is correlated with a type-1 cytokine response

- Pleasance, Jill, Wiedosari, E., Raadsma, Herman, Meeusen, Els, Piedrafita, David

  • Authors: Pleasance, Jill , Wiedosari, E. , Raadsma, Herman , Meeusen, Els , Piedrafita, David
  • Date: 2011
  • Type: Text , Journal article
  • Relation: Parasite Immunology Vol. 33, no. 9 (2011), p. 495-505
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  • Description: Indonesian thin-tail (ITT) sheep can resist infection with Fasciola gigantica but not F. hepatica and presents an ideal model to investigate the mechanisms of liver fluke resistance in a natural host. This study examines the local and systemic immune responses of sheep during Fasciola infection and demonstrates that different anatomical tissues display distinct cytokine profiles consistent with liver fluke migration. The study also reveals a significant difference in the cytokine and antibody profiles of ITT sheep infected with F. gigantica compared with F. hepatica, with a higher ratio of IL-4/IFN-

Streptococcus pneumoniae and Haemophilus influenzae in paediatric meningitis patients at Goroka General Hospital, Papua New Guinea : Serotype distribution and antimicrobial susceptibility in the pre-vaccine era

- Greenhill, Andrew, Phuanukoonnon, Suparat, Michael, Audrey, Yoannes, Mition, Orami, Tilda, Smith, Helen, Murphy, Denise, Blyth, Christopher, Reeder, John, Siba, Peter, Pomat, William, Lehmann, Deborah

  • Authors: Greenhill, Andrew , Phuanukoonnon, Suparat , Michael, Audrey , Yoannes, Mition , Orami, Tilda , Smith, Helen , Murphy, Denise , Blyth, Christopher , Reeder, John , Siba, Peter , Pomat, William , Lehmann, Deborah
  • Date: 2015
  • Type: Text , Journal article
  • Relation: BMC Infectious Diseases Vol. 15, no. 485 (2015), p. 1-8
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  • Description: Background: Bacterial meningitis remains an important infection globally, with the greatest burden in children in low-income settings, including Papua New Guinea (PNG). We present serotype, antimicrobial susceptibility and outcome data from paediatric meningitis patients prior to introduction of Haemophilus influenzae type b (Hib) and pneumococcal conjugate vaccines (PCVs) in PNG, providing a baseline for evaluation of immunisation programs. Methods: Cerebrospinal fluid (CSF) was collected from children admitted to Goroka General Hospital with suspected meningitis between 1996 and 2005. Culture and sensitivity was conducted, and pneumococci and H. influenzae were serotyped. Laboratory findings were linked to clinical outcomes. Results: We enrolled 1884 children. A recognised pathogen was identified in 375 children (19.9%). Streptococcus pneumoniae (n = 180) and Hib (n = 153) accounted for 88.8% of pathogens isolated. 24 different pneumococcal serogroups were identified; non-PCV types 2, 24 and 46 accounted for 31.6% of pneumococcal meningitis. 10- and 13-valent PCVs would cover 44.1% and 45.4% of pneumococcal meningitis respectively. Pneumococcal isolates were commonly resistant to penicillin (21.5%) and 23% of Hib isolates were simultaneously resistant to ampicillin, co-trimoxazole and chloramphenicol. The case fatality rate in patients with a recognised bacterial pathogen was 13.4% compared to 8.5% in culture-negative patients. Conclusions: If implemented in routine expanded programme of immunisation (EPI) with high coverage, current PCVs could prevent almost half of pneumococcal meningitis cases. Given the diversity of circulating serotypes in PNG serotype replacement is of concern. Ongoing surveillance is imperative to monitor the impact of vaccines. In the longer term vaccines providing broader protection against pneumococcal meningitis will be needed. © 2015 Greenhill et al.

Temporal regulation of natural Killer T cell interferon gamma responses by β-catenin-dependent and -independent Wnt signaling

- Kling, Jessica, Jordan, Margaret, Pitt, Lauren, Meiners, Jana, Thanh-Tran, Thao, Tran, Le Son, Nguyen, Tam, Mittal, Deepak, Villani, Rehan, Steptoe, Raymond, Khosrotehrani, Kiarash, Berzins, Stuart, Baxter, Alan, Godrey, Dale, Blumental, Antje

  • Authors: Kling, Jessica , Jordan, Margaret , Pitt, Lauren , Meiners, Jana , Thanh-Tran, Thao , Tran, Le Son , Nguyen, Tam , Mittal, Deepak , Villani, Rehan , Steptoe, Raymond , Khosrotehrani, Kiarash , Berzins, Stuart , Baxter, Alan , Godrey, Dale , Blumental, Antje
  • Date: 2018
  • Type: Text , Journal article
  • Relation: Frontiers in Immunology Vol. 9, no. (2018), p. 1-13
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  • Description: Natural killer T (NKT) cells are prominent innate-like lymphocytes in the liver with critical roles in immune responses during infection, cancer, and autoimmunity. Interferon gamma (IFN-γ) and IL-4 are key cytokines rapidly produced by NKT cells upon recognition of glycolipid antigens presented by antigen-presenting cells (APCs). It has previously been reported that the transcriptional coactivator β-catenin regulates NKT cell differentiation and functionally biases NKT cell responses toward IL-4, at the expense of IFN-γ production. β-Catenin is not only a central effector of Wnt signaling but also contributes to other signaling networks. It is currently unknown whether Wnt ligands regulate NKT cell functions. We thus investigated how Wnt ligands and β-catenin activity shape liver NKT cell functions in vivo in response to the glycolipid antigen, α-galactosylceramide (α-GalCer) using a mouse model. Pharmacologic targeting of β-catenin activity with ICG001, as well as myeloid-specific genetic ablation of Wntless (Wls), to specifically target Wnt protein release by APCs, enhanced early IFN-γ responses. By contrast, within several hours of α-GalCer challenge, myeloid-specific Wls deficiency, as well as pharmacologic targeting of Wnt release using the small molecule inhibitor IWP-2 impaired α-GalCer-induced IFN-γ responses, independent of β-catenin activity. These data suggest that myeloid cell-derived Wnt ligands drive early Wnt/β-catenin signaling that curbs IFN-γ responses, but that, subsequently, Wnt ligands sustain IFN-γ expression independent of β-catenin activity. Our analyses in ICG001-treated mice confirmed a role for β-catenin activity in driving early IL-4 responses by liver NKT cells. However, neither pharmacologic nor genetic perturbation of Wnt production affected the IL-4 response, suggesting that IL-4 production by NKT cells in response to α-GalCer is not driven by released Wnt ligands. Collectively, these data reveal complex temporal roles of Wnt ligands and β-catenin signaling in the regulation of liver NKT cell activation, and highlight Wnt-dependent and -independent contributions of β-catenin to NKT cell functions.
  • Description: Natural killer T (NKT) cells are prominent innate-like lymphocytes in the liver with critical roles in immune responses during infection, cancer, and autoimmunity. Interferon gamma (IFN-

Clonal origins of Vibrio cholerae O1 El Tor strains, Papua New Guinea, 2009-2011

- Horwood, Paul, Collins, Deirdre, Jonduo, Marinjho, Rosewell, Alexander, Dutta, Samir, Dagina, Rosheila, Ropa, Berry, Siba, Peter, Greenhill, Andrew

In vitro generation and characterisation of an influenza B variant with reduced sensitivity to neuraminidase inhibitors

- Cheam, Ai Lee, Barr, Ian, Hampson, Alan, Mosse, Jennifer, Hurt, Aeron

  • Authors: Cheam, Ai Lee , Barr, Ian , Hampson, Alan , Mosse, Jennifer , Hurt, Aeron
  • Date: 2004
  • Type: Text , Journal article
  • Relation: Antiviral Research Vol. 63, no. 3 (2004), p. 177-181
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  • Description: A contemporary influenza type B virus was passaged in vitro in the presence of increasing concentrations of the neuraminidase inhibitors, zanamivir and oseltamivir carboxylate (0.1-1000 μM over nine passages). After the fifth passage in the presence of zanamivir (10 μM), the virus acquired a Glu 119 Asp neuraminidase mutation (influenza A N2 subtype numbering) in the enzyme active site. After a further three passages, in which growth occurred in 100 μM of zanamivir, a Gln 218 Lys mutation (A (H3) numbering) in the HA1 domain of the haemagglutinin was found. In a fluorescence-based neuraminidase inhibition assay, viruses with the Glu 119 Asp NA mutation had a 32,000-fold reduction in sensitivity to the NA inhibitor zanamivir compared to the wild-type virus, while the mutation resulted in a 105-fold reduction in sensitivity to oseltamivir carboxylate. Viruses grown in the presence of 1000 μM oseltamivir carboxylate did not acquire any neuraminidase mutations but did have a His 103 Gln substitution (A (H3) numbering) in the HA1 region of the haemagglutinin which was demonstrated to significantly reduce receptor binding strength in vitro. Tissue culture assays demonstrated that the HA mutation caused a seven-fold reduction in sensitivity to oseltamivir carboxylate, and a 90-fold reduction in sensitivity to zanamivir.

Assessing the anthelmintic activity of pyrazole-5-carboxamide derivatives against Haemonchus contortus

- Jiao, Yaqing, Preston, Sarah, Song, Hongjian, Jabbar, Abdul, Liu, Yuxiu, Baell, Jonathan, Hofmann, Andreas, Hutchinson, Dana, Wang, Tao, Koehler, Anson, Fisher, Gillian, Andrews, Katherine, Laleu, Benoit, Palmer, Michael, Burrows, Jeremy, Wells, Timothy, Wang, Qingmin, Gasser, Robin

  • Authors: Jiao, Yaqing , Preston, Sarah , Song, Hongjian , Jabbar, Abdul , Liu, Yuxiu , Baell, Jonathan , Hofmann, Andreas , Hutchinson, Dana , Wang, Tao , Koehler, Anson , Fisher, Gillian , Andrews, Katherine , Laleu, Benoit , Palmer, Michael , Burrows, Jeremy , Wells, Timothy , Wang, Qingmin , Gasser, Robin
  • Date: 2017
  • Type: Text , Journal article
  • Relation: Parasites and Vectors Vol. 10, no. 1 (2017), p. 1-7
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  • Description: Background: In this study, we tested five series of pyrazole-5-carboxamide compounds (n = 55) for activity against parasitic stages of the nematode Haemonchus contortus (barber’s pole worm), one of the most pathogenic parasites of ruminants. Methods: In an optimised, whole-organism screening assay, using exsheathed third-stage (xL3) and fourth-stage (L4) larvae, we measured the inhibition of larval motility and development of H. contortus. Results: Amongst the 55 compounds, we identified two compounds (designated a-15 and a-17) that reproducibly inhibit xL3 motility as well as L4 motility and development, with IC50 values ranging between ~3.4 and 55.6 μM. We studied the effect of these two ‘hit’ compounds on mitochondrial function by measuring oxygen consumption. This assessment showed that xL3s exposed to each of these compounds consumed significantly less oxygen and had less mitochondrial activity than untreated xL3s, which was consistent with specific inhibition of complex I of the respiratory electron transport chain in arthropods. Conclusions: The present findings provide a sound basis for future work, aimed at identifying the targets of compounds a-15 and a-17 and establishing the modes of action of these chemicals in H. contortus. © 2017 The Author(s).

Arylpyrrole and fipronil analogues that inhibit the motility and/or development of Haemonchus contortus in vitro

- Herath, Dilrukshi, Song, Hongjian, Preston, Sarah, Jabbar, Abdul, Wang, Tao, McGee, Sean, Hofmann, Andreas, Garcia-Bustos, Jose, Chang, Bill, Koehler, Anson, Liu, Yuxiu, Ma, Qiaoqiao, Zhang, Penqxiang, Zhao, Qiqi, Wang, Qingmin, Gasser, Robin

Detection of enteric viral and bacterial pathogens associated with paediatric diarrhoea in Goroka, Papua New Guinea

- Soli, Kevin, Maure, Tobias, Kas, Monalisa, Bande, Grace, Bebes, Sauli, Luang-Suarkia, Dagwin, Siba, Peter, Morita, Ayako, Umezaki, Masahiro, Greenhill, Andrew, Horwood, Paul

  • Authors: Soli, Kevin , Maure, Tobias , Kas, Monalisa , Bande, Grace , Bebes, Sauli , Luang-Suarkia, Dagwin , Siba, Peter , Morita, Ayako , Umezaki, Masahiro , Greenhill, Andrew , Horwood, Paul
  • Date: 2014
  • Type: Text , Journal article
  • Relation: International Journal of Infectious Diseases Vol. 27, no. (2014), p. 54-58
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  • Description: Objectives: The aim of this study was to investigate the viral and bacterial causes of acute watery diarrhoea in hospitalized children in Papua New Guinea. Methods: A retrospective analysis was conducted on stool samples collected from 199 children (age > 5 years) admitted to the paediatric ward of Goroka General Hospital from August 2009 through November 2010. A large range of viral and bacterial enteric pathogens were targeted using real-time PCR/RT-PCR assays. Results: Young children were much more likely to be admitted with acute gastroenteritis, with 62.8% of patients aged >1 year and 88.4% aged >2 years. An enteric pathogen was detected in 69.8% (n= 138) of patients. The most commonly detected pathogens were Shigella spp (26.6%), rotavirus (25.6%), adenovirus types 40/41 (11.6%), enterotoxigenic Escherichia coli (11.1%), enteropathogenic E. coli (8.5%), norovirus G2 (6.0%), and Campylobacter spp (4.0%). Norovirus G1, sapovirus, and Salmonella spp were also detected, but below our statistical limit of detection. Vibrio cholerae and astrovirus were not detected in any patients. Mixed infections were detected in 22.1% of patients, with Shigella and rotavirus most commonly detected in co-infections with other pathogens. Conclusions: This study demonstrates that Shigella and rotavirus are the major pathogens associated with acute paediatric gastroenteritis in this setting. © 2014 The Authors.

Phenotypic screening of the 'Kurz-box' of chemicals identifies two compounds (BLK127 and HBK4) with anthelmintic activity in vitro against parasitic larval stages of Haemonchus contortus

- Nguyen, Linh, Kurz, Thomas, Preston, Sarah, Brueckmann, Hjoerdis, Lungerich, Beate, Herath, Dilrukshi, Koehler, Anson, Wang, Tao, Skalova, Lenka, Jabbar, Abdul, Gasser, Robin

  • Authors: Nguyen, Linh , Kurz, Thomas , Preston, Sarah , Brueckmann, Hjoerdis , Lungerich, Beate , Herath, Dilrukshi , Koehler, Anson , Wang, Tao , Skalova, Lenka , Jabbar, Abdul , Gasser, Robin
  • Date: 2019
  • Type: Text , Journal article
  • Relation: Parasites & Vectors Vol. 12, no. (2019), p. 1-9
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  • Description: BackgroundDue to anthelmintic resistance problems, there is a need to discover and develop new drugs for the treatment and control of economically important and pathogenic nematodes of livestock animals. With this focus in mind, we screened 236 compounds from a library (called the Kurz-box') representing chemically diverse classes such as heterocyclic compounds (e.g. thiazoles, pyrroles, quinolines, pyrimidines, benzo[1,4]diazepines), hydoxamic acid-based metalloenzyme inhibitors, peptidomimetics (bis- and tris-pyrimidoneamides, alkoxyamides) and various intermediates on Haemonchus contortus, one of the most important parasitic nematodes of ruminants.MethodsIn the present study, we tested these compounds, and measured the inhibition of larval motility and development of exsheathed third-stage (xL3) and fourth-stage (L4) larvae of H. contortus using an optimised, whole-organism phenotypic screening assay.ResultsOf the 236 compounds, we identified two active compounds (called BLK127 and HBK4) that induced marked phenotypic changes in the worm in vitro. Compound BLK127 induced an eviscerated' phenotype in the xL3 stage and also inhibited L4 development. Compound HBK4 exerted a curved' phenotype in both xL3s and L4s.ConclusionsThe findings from this study provide a basis for future work on the chemical optimisation of these compounds, on assessing the activity of optimised compounds on adult stages of H. contortus both in vitro and in vivo (in the host animal) and against other parasitic worms of veterinary and medical importance.

Spatio-temporal epidemiology of the cholera outbreak in Papua New Guinea, 2009-2011

- Horwood, Paul, Karl, Stephan, Mueller, Ivo, Jonduo, Marinjho, Pavlin, Boris, Dagina, Rosheila, Ropa, Berry, Bieb, Sibauk, Rosewell, Alexander, Umezaki, Masahiro, Siba, Peter, Greenhill, Andrew

  • Authors: Horwood, Paul , Karl, Stephan , Mueller, Ivo , Jonduo, Marinjho , Pavlin, Boris , Dagina, Rosheila , Ropa, Berry , Bieb, Sibauk , Rosewell, Alexander , Umezaki, Masahiro , Siba, Peter , Greenhill, Andrew
  • Date: 2014
  • Type: Text , Journal article
  • Relation: BMC Infectious Diseases Vol. 14, no. 1 (2014), p.
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  • Description: Background: Cholera continues to be a devastating disease in many developing countries where inadequate safe water supply and poor sanitation facilitate spread. From July 2009 until late 2011 Papua New Guinea experienced the first outbreak of cholera recorded in the country, resulting in > 15,500 cases and > 500 deaths. Methods: Using the national cholera database, we analysed the spatio-temporal distribution and clustering of the Papua New Guinea cholera outbreak. The Kulldorff space-time permutation scan statistic, contained in the software package SatScan v9.2 was used to describe the first 8 weeks of the outbreak in Morobe Province before cholera cases spread throughout other regions of the country. Data were aggregated at the provincial level to describe the spread of the disease to other affected provinces. Results: Spatio-temporal and cluster analyses revealed that the outbreak was characterized by three distinct phases punctuated by explosive propagation of cases when the outbreak spread to a new region. The lack of road networks across most of Papua New Guinea is likely to have had a major influence on the slow spread of the disease during this outbreak. Conclusions: Identification of high risk areas and the likely mode of spread can guide government health authorities to formulate public health strategies to mitigate the spread of the disease through education campaigns, vaccination, increased surveillance in targeted areas and interventions to improve water, sanitation and hygiene.

Respiratory viral pathogens associated with lower respiratory tract disease among young children in the highlands of Papua New Guinea

- Chidlow, Glenys, Laing, Ingrid, Harnett, Gerald, Greenhill, Andrew, Phuanukoonnon, Suparat, Siba, Peter, Pomat, William, Shellam, Geoffrey, Smith, David, Lehmann, Deborah

  • Authors: Chidlow, Glenys , Laing, Ingrid , Harnett, Gerald , Greenhill, Andrew , Phuanukoonnon, Suparat , Siba, Peter , Pomat, William , Shellam, Geoffrey , Smith, David , Lehmann, Deborah
  • Date: 2012
  • Type: Text , Journal article
  • Relation: Journal of Clinical Virology Vol. 54, no. 3 (2012), p. 235-239
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  • Description: 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.

Influenza viruses with B/Yamagata- and B/Victoria-like neuraminidases are differentially affected by mutations that alter antiviral susceptibility

- Farrukee, Rubaiyea, Leang, Sookkwan, Butler, Jeff, Lee, Raphael, Maurer-Stroh, Sebastian, Tilmanis, Danielle, Sullivan, Sheena, Mosse, Jennifer, Barr, Ian, Hurt, Aeron

  • Authors: Farrukee, Rubaiyea , Leang, Sookkwan , Butler, Jeff , Lee, Raphael , Maurer-Stroh, Sebastian , Tilmanis, Danielle , Sullivan, Sheena , Mosse, Jennifer , Barr, Ian , Hurt, Aeron
  • Date: 2015
  • Type: Text , Journal article
  • Relation: Journal of Antimicrobial Chemotherapy Vol. 70, no. 7 (2015), p. 2004-2012
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  • Description: Objectives: The burden of disease due to influenza B is often underestimated. Clinical studies have shown that oseltamivir, a widely used neuraminidase inhibitor (NAI) antiviral drug, may have reduced effectiveness against influenza B viruses. Therefore, it is important to study the effect of neuraminidase mutations in influenza B viruses that may further reduce NAI susceptibility, and to determine whether these mutations have the same effect in the two lineages of influenza B viruses that are currently circulating (B/Yamagata-like and B/Victoria-like). Methods: We characterized the effect of 16 amino acid substitutions across five framework residues and four monomeric interface residues on the susceptibility to four different NAIs (oseltamivir, zanamivir, peramivir and laninamivir). Results: Framework residue mutations E117A and E117G conferred highly reduced inhibition to three of the four NAIs, but substantially reduced neuraminidase activity, whereas other framework mutations retained a greater level of NA activity. Mutations E105K, P139S and G140R of the monomeric interface were also found to cause highly reduced inhibition, but, interestingly, their effect was substantially greater in a B/Victoria-like neuraminidase than in a B/Yamagata-like neuraminidase, with some susceptibility values being up to 1000-fold different between lineages. Conclusions: The frequency and the effect of key neuraminidase mutations on neuraminidase activity and NAI susceptibility can differ substantially between the two influenza B lineages. Therefore, future surveillance, analysis and interpretation of influenza B virus NAI susceptibility should consider the B lineage of the neuraminidase in the same manner as already occurs for different influenza A neuraminidase subtypes.

Health challenges of the pacific region : Insights from history, geography, social determinants, genetics, and the microbiome

- Horwood, Paul, Tarantola, Arnaud, Goarant, Cyrille, Matsui, Mariko, Klement, Elise, Umezaki, Masahiro, Navarro, Severine, Greenhill, Andrew

  • Authors: Horwood, Paul , Tarantola, Arnaud , Goarant, Cyrille , Matsui, Mariko , Klement, Elise , Umezaki, Masahiro , Navarro, Severine , Greenhill, Andrew
  • Date: 2019
  • Type: Text , Journal article , Review
  • Relation: Frontiers in Immunology Vol. 10, no. (2019), p. 1-16
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  • Description: The Pacific region, also referred to as Oceania, is a geographically widespread region populated by people of diverse cultures and ethnicities. Indigenous people in the region (Melanesians, Polynesians, Micronesians, Papuans, and Indigenous Australians) are over-represented on national, regional, and global scales for the burden of infectious and non-communicable diseases. Although social and environmental factors such as poverty, education, and access to health-care are assumed to be major drivers of this disease burden, there is also developing evidence that genetic and microbiotic factors should also be considered. To date, studies investigating genetic and/or microbiotic links with vulnerabilities to infectious and non-communicable diseases have mostly focused on populations in Europe, Asia, and USA, with uncertain associations for other populations such as indigenous communities in Oceania. Recent developments in personalized medicine have shown that identifying ethnicity-linked genetic vulnerabilities can be important for medical management. Although our understanding of the impacts of the gut microbiome on health is still in the early stages, it is likely that equivalent vulnerabilities will also be identified through the interaction between gut microbiome composition and function with pathogens and the host immune system. As rapid economic, dietary, and cultural changes occur throughout Oceania it becomes increasingly important that further research is conducted within indigenous populations to address the double burden of high rates of infectious diseases and rapidly rising non-communicable diseases so that comprehensive development goals can be planned. In this article, we review the current knowledge on the impact of nutrition, genetics, and the gut microbiome on infectious diseases in indigenous people of the Pacific region.

Increasing chloramphenicol resistance in Streptococcus pneumoniae isolates from Papua New Guinean Children with acute bacterial meningitis

- Manning, Laurens, Laman, Moses, Greenhill, Andrew, Michael, Audrey, Siba, Peter, Mueller, Ivo, Davis, Timothy