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TM9/Phg1 and SadA proteins control surface expression and stability of SibA adhesion molecules in Dictyostelium

Romain Froquet, Marion le Coadic, Jackie Perrin, Nathalie Cherix, Sophie Cornillon, Pierre Cosson, Peter Van Haastert
2012 Molecular Biology of the Cell  
This is due to a decrease in sibA mRNA levels, in SibA protein stability, and in SibA targeting to the cell surface.  ...  A contact site A (csA)-SibA chimeric protein comprising only the transmembrane and cytosolic domains of SibA and the extracellular domain of the Dictyostelium surface protein csA also showed reduced stability  ...  of SibA.  ... 
doi:10.1091/mbc.e11-04-0338 pmid:22219373 pmcid:PMC3279395 fatcat:oyd7bth4uzb2hjckqlrm3h3bae

Evaluation of Serological Diagnostic Tests for Typhoid Fever in Papua New Guinea Using a Composite Reference Standard

Valentine Siba, Paul F. Horwood, Kilagi Vanuga, Johanna Wapling, Rebecca Sehuko, Peter M. Siba, Andrew R. Greenhill
2012 Clinical and Vaccine Immunology  
ABSTRACTTyphoid fever remains a major global health problem. A major impediment to improving outcomes is the lack of appropriate diagnostic tools, which have not significantly improved in low-income settings for 100 years. We evaluated two commercially available rapid diagnostic tests (Tubex and TyphiDot), a prototype (TyphiRapid TR-02), and the commonly used single-serum Widal test in a previously reported high-burden area of Papua New Guinea. Samples were collected from 530 outpatients with
more » ... illary temperatures of ≥37.5°C, and analysis was conducted on all malaria-negative samples (n= 500). A composite reference standard of blood culture and PCR was used, by which 47 participants (9.4%) were considered typhoid fever positive. The sensitivity and specificity of the Tubex (51.1% and 88.3%, respectively) and TyphiDot (70.0% and 80.1%, respectively) tests were not high enough to warrant their ongoing use in this setting; however, the sensitivity and specificity for the TR-02 prototype were promising (89.4% and 85.0%, respectively). An axillary temperature of ≥38.5°C correlated with typhoid fever (P= 0.014). With an appropriate diagnostic test, conducting typhoid fever diagnosis only on patients with high-grade fever could dramatically decrease the costs associated with diagnosis while having no detrimental impact on the ability to accurately diagnose the illness.
doi:10.1128/cvi.00380-12 pmid:22993409 pmcid:PMC3491554 fatcat:wz2sguy43jdg3le7an2nznih5y

Strategies for Detection of Plasmodium species Gametocytes

Rahel Wampfler, Felistas Mwingira, Sarah Javati, Leanne Robinson, Inoni Betuela, Peter Siba, Hans-Peter Beck, Ivo Mueller, Ingrid Felger, Rick Edward Paul
2013 PLoS ONE  
Carriage and density of gametocytes, the transmission stages of malaria parasites, are determined for predicting the infectiousness of humans to mosquitoes. This measure is used for evaluating interventions that aim at reducing malaria transmission. Gametocytes need to be detected by amplification of stage-specific transcripts, which requires RNA-preserving blood sampling. For simultaneous, highly sensitive quantification of both, blood stages and gametocytes, we have compared and optimized
more » ... erent strategies for field and laboratory procedures in a cross sectional survey in 315 5-9 yr old children from Papua New Guinea. qRT-PCR was performed for gametocyte markers pfs25 and pvs25, Plasmodium species prevalence was determined by targeting both, 18S rRNA genes and transcripts. RNA-based parasite detection resulted in a P. falciparum positivity of 24.1%; of these 40.8% carried gametocytes. P. vivax positivity was 38.4%, with 38.0% of these carrying gametocytes. Sensitivity of DNA-based parasite detection was substantially lower with 14.1% for P. falciparum and 19.6% for P. vivax. Using the lower DNAbased prevalence of asexual stages as a denominator increased the percentage of gametocyte-positive infections to 59.1% for P. falciparum and 52.4% for P. vivax. For studies requiring highly sensitive and simultaneous quantification of sexual and asexual parasite stages, 18S rRNA transcript-based detection saves efforts and costs. RNA-based positivity is considerably higher than other methods. On the other hand, DNA-based parasite quantification is robust and permits comparison with other globally generated molecular prevalence data. Molecular monitoring of low density asexual and sexual parasitaemia will support the evaluation of effects of up-scaled antimalarial intervention programs and can also inform about small scale spatial variability in transmission intensity.
doi:10.1371/journal.pone.0076316 pmid:24312682 pmcid:PMC3848260 fatcat:thdzl7cbh5gmzd7o5hf3k2qam4

Antibiotic resistant Shigella is a major cause of diarrhoea in the Highlands of Papua New Guinea

Andrew R Greenhill, Carlton Guwada, Valentine Siba, Audrey Michael, Mition Yoannes, Yolandah Wawarie, Rebecca Ford, Peter M Siba, Paul F Horwood
2014 Journal of Infection in Developing Countries  
Diarrhoea remains a major cause of illness in Papua New Guinea (PNG); however, little is known about its aetiology. As a result of the cholera outbreak that spread throughout PNG in 2009-2011, we conducted diarrhoeal surveillance in Eastern Highlands Province. Methodology: Following informed consent and a brief questionnaire, participants provided a stool sample or duplicate rectal swabs. Samples were tested for common bacterial pathogens Salmonella spp., Shigella spp., Vibrio spp.,
more » ... r spp. and Yersinia enterocolitica using established culture methods. Enteric parasites were detected using microscopy. Results: A total of 216 participants were enrolled; where age was recorded, 42% were under 5 years of age, 6.7% were 5 to 17 years of age and 51.3% ≥18 years of age. One or more pathogens were detected in 68 (31.5%) participants, with Shigella (primarily S. flexneri) being the most commonly isolated (47 of 216 participants). Enteric parasites were detected in 23 of the 216 participants, occurring as a co-infection with another pathogen in 12 of 23 cases. No Vibrio cholerae was detected. Shigella isolates were commonly resistant to ampicillin, tetracycline, co-trimoxazole and chloramphenicol. Conclusions: Shigellae, specifically S. flexneri, are important pathogens in the highlands of PNG. While most studies in low-income settings focus on childhood aetiology, we have demonstrated the importance of Shigella in both children and adults. Enteric parasites remain present and presumably contribute to the burden of gastrointestinal illness. While improvements in sanitation and hygiene would help lower the burden of all aetiologies of infectious diarrhoea, additional control strategies targeting Shigella may also be warranted.
doi:10.3855/jidc.4396 pmid:25390051 fatcat:t3aedwvw45abdhqmvfv5aecx4e

Novel Genotyping Tools for Investigating Transmission Dynamics of Plasmodium falciparum

Rahel Wampfler, Lincoln Timinao, Hans-Peter Beck, Issiaka Soulama, Alfred B. Tiono, Peter Siba, Ivo Mueller, Ingrid Felger
2014 Journal of Infectious Diseases  
Background. Differentiation between gametocyte-producing Plasmodium falciparum clones depends on both high levels of stage-specific transcripts and high genetic diversity of the selected genotyping marker obtained by a high-resolution typing method. By analyzing consecutive samples of one host, the contribution of each infecting clone to transmission and the dynamics of gametocyte production in multiclone infections can be studied. Methods. We have evaluated capillary electrophoresis based
more » ... rentiation of 6 length-polymorphic gametocyte genes. RNA and DNA of 25 µL whole blood from 46 individuals from Burkina Faso were simultaneously genotyped. Results. Highest discrimination power was achieved by pfs230 with 18 alleles, followed by pfg377 with 15 alleles. When assays were performed in parallel on RNA and DNA, 85.7% of all pfs230 samples and 59.5% of all pfg377 samples contained at least one matching genotype in DNA and RNA. Conclusions. The imperfect detection in both, DNA and RNA, was identified as major limitation for investigating transmission dynamics, owing primarily to the volume of blood processed and the incomplete representation of all clones in the sample tested. Abundant low-density gametocyte carriers impede clone detectability, which may be improved by analyzing larger volumes and detecting initially sequestered gametocyte clones in follow-up samples.
doi:10.1093/infdis/jiu236 pmid:24771862 pmcid:PMC4271069 fatcat:r5jecrzgz5ftbmuvh6dcvh5rdq

Malaria epidemiology in Lihir Island, Papua New Guinea

Oriol Mitjà, Raymond Paru, Billy Selve, Inoni Betuela, Peter Siba, Elisa De Lazzari, Quique Bassat
2013 Malaria Journal  
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
more » ... er the intervention (2006)(2007)(2008)(2009)(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.
doi:10.1186/1475-2875-12-98 pmid:23497296 pmcid:PMC3606355 fatcat:x6nxts3edfb57kntcmh5bk2lq4

Population genomics of the filarial nematode parasite Wuchereria bancrofti from mosquitoes

Scott T. Small, Lisa J. Reimer, Daniel J. Tisch, Christopher L. King, Bruce M. Christensen, Peter M. Siba, James W. Kazura, David Serre, Peter A. Zimmerman
2016 Molecular Ecology  
However we postulate that the ongoing Wb elimination programs as well as other factors such as heavy malaria pressure in the north coastal lowlands (Peters & Christian 1960a ) and malaria elimination  ...  programs using bed-nets and insecticides (Peters & Christian 1960b; Parkinson 1974; Spencer et al. 1974) has driven the N e of Wb in PNG to be even lower than the most recent estimate obtained from MSMC  ... 
doi:10.1111/mec.13574 pmid:26850696 pmcid:PMC4808423 fatcat:ogapyvauk5g2zbw7parimiyq4y

Experimental avian paramyxovirus serotype-3 infection in chickens and turkeys

Sachin Kumar, Flavia Militino Dias, Baibaswata Nayak, Peter L. Collins, Siba K. Samal
2010 Veterinary Research  
Avian paramyxoviruses (APMV) are divided into nine serotypes. Newcastle disease virus (APMV-1) is the most extensively characterized, while relatively little information is available for the other APMV serotypes. In the present study, we examined the pathogenicity of two divergent strains of APMV-3, Netherlands and Wisconsin, in (i) 9-day-old embryonated chicken eggs, (ii) 1-day-old specific pathogen free (SPF) chicks and turkeys, and (iii) 2-week-old SPF chickens and turkeys. The mean death
more » ... e in 9-day-old embryonated chicken eggs was 112 h for APMV-3 strain Netherlands and > 168 h for strain Wisconsin. The intracerebral pathogenicity index in 1-day-old chicks for strain Netherlands was 0.39 and for strain Wisconsin was zero. Thus, both strains are lentogenic. Both the strains replicated well in brain tissue when inoculated intracerebrally in 1-day-old SPF chicks, but without causing death. Mild respiratory disease signs were observed in 1-day-old chickens and turkeys when inoculated through oculonasal route with either strain. There were no overt signs of illness in 2-weeks-old chickens and turkeys by either strain, although all the birds seroconverted after infection. The viruses were isolated predominantly from brain, lungs, spleens, trachea, pancreas and kidney. Immunohistochemistry studies also showed the presence of large amount of viral antigens in both epithelial and sub-epithelial lining of respiratory and alimentary tracts. Our result suggests systemic spread of APMV-3 even though the viral fusion glycoprotein does not contain the canonical furin proteases cleavage site. Furthermore, there was little or no disease despite systemic viral spread and abundant viral replication in all the tissues tested. avian paramyxovirus / pathogenicity
doi:10.1051/vetres/2010042 pmid:20663473 pmcid:PMC2939697 fatcat:tuwf2pxcpfdedlax36xwtzbvre

Drug resistance-conferring mutations in Mycobacterium tuberculosis from Madang, Papua New Guinea

Marie Ballif, Paul Harino, Serej Ley, Mireia Coscolla, Stefan Niemann, Robyn Carter, Christopher Coulter, Sonia Borrell, Peter Siba, Suparat Phuanukoonnon, Sebastien Gagneux, Hans-Peter Beck
2012 BMC Microbiology  
Hans-Peter Beck participated in the design of the study, coordinated the molecular work and helped to draft the manuscript. All authors read and approved the final manuscript.  ...  Authors' information Co-senior author: Sebastien Gagneux and Hans-Peter Beck. Figure 1 1 List of all mutations observed in each of the 27 strains resistant to at least one drug.  ... 
doi:10.1186/1471-2180-12-191 pmid:22943573 pmcid:PMC3478209 fatcat:2t4j5ty3izcrdojnlrgfw5bjru

Unbiased Characterization of Anopheles Mosquito Blood Meals by Targeted High-Throughput Sequencing

Kyle Logue, John Bosco Keven, Matthew V. Cannon, Lisa Reimer, Peter Siba, Edward D. Walker, Peter A. Zimmerman, David Serre, Margaret Kosek
2016 PLoS Neglected Tropical Diseases  
Understanding mosquito host choice is important for assessing vector competence or identifying disease reservoirs. Unfortunately, the availability of an unbiased method for comprehensively evaluating the composition of insect blood meals is very limited, as most current molecular assays only test for the presence of a few pre-selected species. These approaches also have limited ability to identify the presence of multiple mammalian hosts in a single blood meal. Here, we describe a novel
more » ... oughput sequencing method that enables analysis of 96 mosquitoes simultaneously and provides a comprehensive and quantitative perspective on the composition of each blood meal. We validated in silico that universal primers targeting the mammalian mitochondrial 16S ribosomal RNA genes (16S rRNA) should amplify more than 95% of the mammalian 16S rRNA sequences present in the NCBI nucleotide database. We applied this method to 442 female Anopheles punctulatus s. l. mosquitoes collected in Papua New Guinea (PNG). While human (52.9%), dog (15.8%) and pig (29.2%) were the most common hosts identified in our study, we also detected DNA from mice, one marsupial species and two bat species. Our analyses also revealed that 16.3% of the mosquitoes fed on more than one host. Analysis of the human mitochondrial hypervariable region I in 102 human blood meals showed that 5 (4.9%) of the mosquitoes unambiguously fed on more than one person. Overall, analysis of PNG mosquitoes illustrates the potential of this approach to identify unsuspected hosts and characterize mixed blood meals, and shows how this approach can be adapted to evaluate inter-individual variations among human blood meals. Furthermore, this approach can be applied to any disease-transmitting arthropod and can be easily customized to investigate non-mammalian host sources. PLOS Neglected Tropical Diseases |
doi:10.1371/journal.pntd.0004512 pmid:26963245 pmcid:PMC4786206 fatcat:sdelruzzrbgxrpmyhdokbunrx4

Do penile cutting practices other than full circumcision protect against HIV?

John M Kaldor, David MacLaren, John McBride, Peter Siba, Andrew Vallely
2014 BMC Infectious Diseases  
doi:10.1186/1471-2334-14-s2-p17 pmcid:PMC4220885 fatcat:ssykd5hirve27mhezp5ogzz2k4

Experimental infection of hamsters with avian paramyxovirus serotypes 1 to 9

Arthur S Samuel, Madhuri Subbiah, Heather Shive, Peter L Collins, Siba K Samal
2011 Veterinary Research  
Avian paramyxoviruses (APMVs) are frequently isolated from domestic and wild birds throughout the world and are separated into nine serotypes (APMV-1 to -9). Only in the case of APMV-1, the infection of non-avian species has been investigated. The APMVs presently are being considered as human vaccine vectors. In this study, we evaluated the replication and pathogenicity of all nine APMV serotypes in hamsters. The hamsters were inoculated intranasally with each virus and monitored for clinical
more » ... sease, pathology, histopathology, virus replication, and seroconversion. On the basis of one or more of these criteria, each of the APMV serotypes was found to replicate in hamsters. The APMVs produced mild or inapparent clinical signs in hamsters except for APMV-9, which produced moderate disease. Gross lesions were observed over the pulmonary surface of hamsters infected with APMV-2 & -3, which showed petechial and ecchymotic hemorrhages, respectively. Replication of all of the APMVs except APMV-5 was confirmed in the nasal turbinates and lungs, indicating a tropism for the respiratory tract. Histologically, the infection resulted in lung lesions consistent with bronchointerstitial pneumonia of varying severity and nasal turbinates with blunting or loss of cilia of the epithelium lining the nasal septa. The majority of APMV-infected hamsters exhibited transient histological lesions that self resolved by 14 days post infection (dpi). All of the hamsters infected with the APMVs produced serotype-specific HI or neutralizing antibodies, confirming virus replication. Taken together, these results demonstrate that all nine known APMV serotypes are capable of replicating in hamsters with minimal disease and pathology.
doi:10.1186/1297-9716-42-38 pmid:21345199 pmcid:PMC3052182 fatcat:gdjjmakkorhuplwdrkiyu6roti

Progress in mosquito net coverage in Papua New Guinea

Manuel W Hetzel, Adnan AK Choudhury, Justin Pulford, Yangta Ura, Maxine Whittaker, Peter M Siba, Ivo Mueller
2014 Malaria Journal  
Since 2004, the Global Fund-supported National Malaria Control Programme of Papua New Guinea (PNG) has been implementing country-wide free long-lasting insecticidal net (LLIN) distribution campaigns. In 2009, after the first distribution, only 32.5% of the population used a LLIN, mainly due to an insufficient number of nets available. This study investigated changes in mosquito net ownership and use following the continued free distribution of LLINs across PNG. Methods: Five villages from each
more » ... rovince and 30 households from each village were randomly sampled in a country-wide household survey in 2010/11. A structured questionnaire administered to household heads recorded information on mosquito net ownership and use alongside household characteristics. Revised ownership and access indicators were applied in the analysis to reveal coverage gaps. Results: The survey covered 1,996 households in 77 villages. Ownership of at least one LLIN was reported by 81.8% of households, compared to 64.6% in 2009 (P = 0.002). Sufficient LLINs to cover all household members (one net per two people) were found in 41.3% of the households (21.4% in 2009, P < 0.001). Of all household members, 61.4% had access to a LLIN within their household (44.3% in 2009 P = 0.002), and 48.3% slept under a LLIN (32.5% in 2009, P = 0.001). LLIN use in children under five years amounted to 58.2%, compared to 39.5% in 2009 (P < 0.001). Significant regional differences in coverage and changes over time were observed. A recent LLIN distribution was a key determinant of LLIN ownership (adj. OR = 3.46) while families in high quality houses would frequently not own a LLIN (adj. OR = 0.09). Residents were more likely to use LLINs than household guests (OR = 2.04). Conclusions: Repeated LLIN distribution has led to significant increases in mosquito net ownership and use with few regional exceptions. Additional nets are required in areas where access is low, while major efforts are required to encourage the use of existing nets in region where access is high but use remains low. Complementary vector control approaches should also be considered in such settings.
doi:10.1186/1475-2875-13-242 pmid:24961245 pmcid:PMC4077150 fatcat:5svtp6v5bbdhfm4vtoixoeaooi

Seeking treatment for symptomatic malaria in Papua New Guinea

Carol P Davy, Elisa Sicuri, Maria Ome, Ellie Lawrence-Wood, Peter Siba, Gordon Warvi, Ivo Mueller, Lesong Conteh
2010 Malaria Journal  
Malaria places a significant burden on the limited resources of many low income countries. Knowing more about why and where people seek treatment will enable policy makers to better allocate the limited resources. This study aims to better understand what influences treatment-seeking behaviour for malaria in one such low-income country context, Papua New Guinea (PNG). Methods: Two culturally, linguistically and demographically different regions in PNG were selected as study sites. A cross
more » ... nal household survey was undertaken in both sites resulting in the collection of data on 928 individuals who reported suffering from malaria in the previous four weeks. A probit model was then used to identify the factors determining whether or not people sought treatment for presumptive malaria. Multinomial logit models also assisted in identifying the factors that determined where people sought treatments.
doi:10.1186/1475-2875-9-268 pmid:20925921 pmcid:PMC2972304 fatcat:y4yvf7mm5neolprprv2p4auxia

Experimental Infection of Mice with Avian Paramyxovirus Serotypes 1 to 9

Sunil K. Khattar, Sachin Kumar, Sa Xiao, Peter L. Collins, Siba K. Samal, Jianming Qiu
2011 PLoS ONE  
The nine serotypes of avian paramyxoviruses (APMVs) are frequently isolated from domestic and wild birds worldwide. APMV-1, also called Newcastle disease virus, was shown to be attenuated in non-avian species and is being developed as a potential vector for human vaccines. In the present study, we extended this evaluation to the other eight serotypes by evaluating infection in BALB/c mice. Mice were inoculated intranasally with a prototype strain of each of the nine serotypes and monitored for
more » ... linical disease, gross pathology, histopathology, virus replication and viral antigen distribution, and seroconversion. On the basis of multiple criteria, each of the APMV serotypes except serotype 5 was found to replicate in mice. Five of the serotypes produced clinical disease and significant weight loss in the following order of severity: 1, 2.6, 9.7. However, disease was short-lived. The other serotypes produced no evident clinical disease. Replication of all of the APMVs except APMV-5 in the nasal turbinates and lungs was confirmed by the recovery of infectious virus and by substantial expression of viral antigen in the epithelial lining detected by immunohistochemistry. Trace levels of infectious APMV-4 and -9 were detected in the brain of some animals; otherwise, no virus was detected in the brain, small intestine, kidney, or spleen. Histologically, infection with the APMVs resulted in lung lesions consistent with broncho-interstitial pneumonia of varying severity that were completely resolved at 14 days post infection. All of the mice infected with the APMVs except APMV-5 produced serotype-specific HI serum antibodies, confirming a lack of replication of APMV-5. Taken together, these results demonstrate that all APMV serotypes except APMV-5 are capable of replicating in mice with minimal disease and pathology. This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
doi:10.1371/journal.pone.0016776 pmid:21347313 pmcid:PMC3037383 fatcat:ycoulynofjf3znymsxywcpirmu
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