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Search Results: 1 - 10 of 321450 matches for " Heiman F. L. Wertheim "
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Key Role for Clumping Factor B in Staphylococcus aureus Nasal Colonization of Humans
Heiman F. L Wertheim ,Evelyn Walsh,Roos Choudhurry,Damian C Melles,lène A. M Boelens,Helen Miajlovic,Henri A Verbrugh,Timothy Foster,Alex van Belkum
PLOS Medicine , 2008, DOI: 10.1371/journal.pmed.0050017
Abstract: Background Staphylococcus aureus permanently colonizes the vestibulum nasi of one-fifth of the human population, which is a risk factor for autoinfection. The precise mechanisms whereby S. aureus colonizes the nose are still unknown. The staphylococcal cell-wall protein clumping factor B (ClfB) promotes adhesion to squamous epithelial cells in vitro and might be a physiologically relevant colonization factor. Methods and Findings We define the role of the staphylococcal cytokeratin-binding protein ClfB in the colonization process by artificial inoculation of human volunteers with a wild-type strain and its single locus ClfB knock-out mutant. The wild-type strain adhered to immobilized recombinant human cytokeratin 10 (CK10) in a dose-dependent manner, whereas the ClfB? mutant did not. The wild-type strain, when grown to the stationary phase in a poor growth medium, adhered better to CK10, than when the same strain was grown in a nutrient-rich environment. Nasal cultures show that the mutant strain is eliminated from the nares significantly faster than the wild-type strain, with a median of 3 ± 1 d versus 7 ± 4 d (p = 0.006). Furthermore, the wild-type strain was still present in the nares of 3/16 volunteers at the end of follow-up, and the mutant strain was not. Conclusions The human colonization model, in combination with in vitro data, shows that the ClfB protein is a major determinant of nasal-persistent S. aureus carriage and is a candidate target molecule for decolonization strategies.
Furious Rabies after an Atypical Exposure
Heiman F. L Wertheim ,Thai Q Nguyen,Kieu Anh T Nguyen,Menno D de Jong,Walter R. J Taylor,Tan V Le,Ha H Nguyen,Hanh T. H Nguyen,Jeremy Farrar,Peter Horby,Hien D Nguyen
PLOS Medicine , 2009, DOI: 10.1371/journal.pmed.1000044
Abstract:
Klebsiella pneumoniae Oropharyngeal Carriage in Rural and Urban Vietnam and the Effect of Alcohol Consumption
Trinh Tuyet Dao, Dror Liebenthal, Toan Khanh Tran, Bich Ngoc Thi Vu, Diep Ngoc Thi Nguyen, Huong Kieu Thi Tran, Chuc Kim Thi Nguyen, Huong Lan Thi Vu, Annette Fox, Peter Horby, Kinh Van Nguyen, Heiman F. L. Wertheim
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0091999
Abstract: Introduction Community acquired K. pneumoniae pneumonia is still common in Asia and is reportedly associated with alcohol use. Oropharyngeal carriage of K. pneumoniae could potentially play a role in the pathogenesis of K. pneumoniae pneumonia. However, little is known regarding K. pneumoniae oropharyngeal carriage rates and risk factors. This population-based cross-sectional study explores the association of a variety of demographic and socioeconomic factors, as well as alcohol consumption with oropharyngeal carriage of K. pneumoniae in Vietnam. Methods and Findings 1029 subjects were selected randomly from age, sex, and urban and rural strata. An additional 613 adult men from a rural environment were recruited and analyzed separately to determine the effects of alcohol consumption. Demographic, socioeconomic, and oropharyngeal carriage data was acquired for each subject. The overall carriage rate of K. pneumoniae was 14.1% (145/1029, 95% CI 12.0%–16.2%). By stepwise logistic regression, K. pneumoniae carriage was found to be independently associated with age (OR 1.03, 95% CI 1.02–1.04), smoking (OR 1.9, 95% CI 1.3–2.9), rural living location (OR 1.6, 95% CI 1.1–2.4), and level of weekly alcohol consumption (OR 1.7, 95% CI 1.04–2.8). Conclusion Moderate to heavy weekly alcohol consumption, old age, smoking, and living in a rural location are all found to be associated with an increased risk of K. pneumoniae carriage in Vietnamese communities. Whether K. pneumoniae carriage is a risk factor for pneumonia needs to be elucidated.
A Long Neglected World Malaria Map: Plasmodium vivax Endemicity in 2010
Peter W. Gething ,Iqbal R. F. Elyazar,Catherine L. Moyes,David L. Smith,Katherine E. Battle,Carlos A. Guerra,Anand P. Patil,Andrew J. Tatem,Rosalind E. Howes,Monica F. Myers,Dylan B. George,Peter Horby,Heiman F. L. Wertheim,Ric N. Price,Ivo Müeller,J. Kevin Baird,Simon I. Hay
PLOS Neglected Tropical Diseases , 2012, DOI: 10.1371/journal.pntd.0001814
Abstract: Background Current understanding of the spatial epidemiology and geographical distribution of Plasmodium vivax is far less developed than that for P. falciparum, representing a barrier to rational strategies for control and elimination. Here we present the first systematic effort to map the global endemicity of this hitherto neglected parasite. Methodology and Findings We first updated to the year 2010 our earlier estimate of the geographical limits of P. vivax transmission. Within areas of stable transmission, an assembly of 9,970 geopositioned P. vivax parasite rate (PvPR) surveys collected from 1985 to 2010 were used with a spatiotemporal Bayesian model-based geostatistical approach to estimate endemicity age-standardised to the 1–99 year age range (PvPR1–99) within every 5×5 km resolution grid square. The model incorporated data on Duffy negative phenotype frequency to suppress endemicity predictions, particularly in Africa. Endemicity was predicted within a relatively narrow range throughout the endemic world, with the point estimate rarely exceeding 7% PvPR1–99. The Americas contributed 22% of the global area at risk of P. vivax transmission, but high endemic areas were generally sparsely populated and the region contributed only 6% of the 2.5 billion people at risk (PAR) globally. In Africa, Duffy negativity meant stable transmission was constrained to Madagascar and parts of the Horn, contributing 3.5% of global PAR. Central Asia was home to 82% of global PAR with important high endemic areas coinciding with dense populations particularly in India and Myanmar. South East Asia contained areas of the highest endemicity in Indonesia and Papua New Guinea and contributed 9% of global PAR. Conclusions and Significance This detailed depiction of spatially varying endemicity is intended to contribute to a much-needed paradigm shift towards geographically stratified and evidence-based planning for P. vivax control and elimination.
Laboratory Capacity Building in Asia for Infectious Disease Research: Experiences from the South East Asia Infectious Disease Clinical Research Network (SEAICRN)
Heiman F. L. Wertheim ,Pilaipan Puthavathana,Ngoc My Nghiem,H. Rogier van Doorn,Trung Vu Nguyen,Hung Viet Pham,Decy Subekti,Syahrial Harun,Suhud Malik,Janet Robinson,Motiur Rahman,Walter Taylor,Niklas Lindegardh,Steve Wignall,Jeremy J. Farrar,Menno D. de Jong
PLOS Medicine , 2010, DOI: 10.1371/journal.pmed.1000231
Abstract:
Immunological and Viral Determinants of Dengue Severity in Hospitalized Adults in Ha Noi, Viet Nam
Annette Fox ,Le Nguyen Minh Hoa,Cameron P. Simmons,Marcel Wolbers,Heiman F. L. Wertheim,Pham Thi Khuong,Tran Thi Hai Ninh,Trinh Thi Minh Lien,Nguyen Thi Lien,Nguyen Vu Trung,Nguyen Duc Hien,Jeremy Farrar,Peter Horby,Walter R. Taylor,Nguyen Van Kinh
PLOS Neglected Tropical Diseases , 2011, DOI: 10.1371/journal.pntd.0000967
Abstract: Background The relationships between the infecting dengue serotype, primary and secondary infection, viremia and dengue severity remain unclear. This cross-sectional study examined these interactions in adult patients hospitalized with dengue in Ha Noi. Methods and Findings 158 patients were enrolled between September 16 and November 11, 2008. Quantitative RT-PCR, serology and NS1 detection were used to confirm dengue infection, determine the serotype and plasma viral RNA concentration, and categorize infections as primary or secondary. 130 (82%) were laboratory confirmed. Serology was consistent with primary and secondary infection in 34% and 61%, respectively. The infecting serotype was DENV-1 in 42 (32%), DENV-2 in 39 (30%) and unknown in 49 (38%). Secondary infection was more common in DENV-2 infections (79%) compared to DENV-1 (36%, p<0.001). The proportion that developed dengue haemorrhagic fever (DHF) was 32% for secondary infection compared to 18% for primary infection (p = 0.14), and 26% for DENV-1 compared to 28% for DENV-2. The time until NS1 and plasma viral RNA were undetectable was shorter for DENV-2 compared to DENV-1 (p≤0.001) and plasma viral RNA concentration on day 5 was higher for DENV-1 (p = 0.03). Plasma viral RNA concentration was higher in secondary infection on day 5 of illness (p = 0.046). We didn't find an association between plasma viral RNA concentration and clinical severity. Conclusion Dengue is emerging as a major public health problem in Ha Noi. DENV-1 and DENV-2 were the prevalent serotypes with similar numbers and clinical presentation. Secondary infection may be more common amongst DENV-2 than DENV-1 infections because DENV-2 infections resulted in lower plasma viral RNA concentrations and viral RNA concentrations were higher in secondary infection. The drivers of dengue emergence in northern Viet Nam need to be elucidated and public health measures instituted.
Streptococcus suis, an Important Cause of Adult Bacterial Meningitis in Northern Vietnam
Heiman F. L. Wertheim, Huyen Nguyen Nguyen, Walter Taylor, Trinh Thi Minh Lien, Hoa Thi Ngo, Thai Quoc Nguyen, Bich Ngoc Thi Nguyen, Ha Hong Nguyen, Ha Minh Nguyen, Cap Trung Nguyen, Trinh Tuyet Dao, Trung Vu Nguyen, Annette Fox, Jeremy Farrar, Constance Schultsz, Hien Duc Nguyen, Kinh Van Nguyen, Peter Horby
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0005973
Abstract: Background Streptococcus suis can cause severe systemic infection in adults exposed to infected pigs or after consumption of undercooked pig products. S. suis is often misdiagnosed, due to lack of awareness and improper testing. Here we report the first fifty cases diagnosed with S. suis infection in northern Viet Nam. Methodology/Principal Findings In 2007, diagnostics for S. suis were set up at a national hospital in Hanoi. That year there were 43 S. suis positive cerebrospinal fluid samples, of which S. suis could be cultured in 32 cases and 11 cases were only positive by PCR. Seven patients were blood culture positive for S. suis but CSF culture and PCR negative; making a total of 50 patients with laboratory confirmed S. suis infection in 2007. The number of S. suis cases peaked during the warmer months. Conclusions/Significance S. suis was commonly diagnosed as a cause of bacterial meningitis in adults in northern Viet Nam. In countries where there is intense and widespread exposure of humans to pigs, S. suis can be an important human pathogen.
Providing Impetus, Tools, and Guidance to Strengthen National Capacity for Antimicrobial Stewardship in Viet Nam
Heiman F. L. Wertheim equal contributor ,Arjun Chandna equal contributor,Phu Dinh Vu,Ca Van Pham,Phong Dai Thi Nguyen,Yen Minh Lam,Chau Vinh Van Nguyen,Mattias Larsson,Ulf Rydell,Lennart E. Nilsson,Jeremy Farrar,Kinh Van Nguyen,H?kan Hanberger
PLOS Medicine , 2013, DOI: 10.1371/journal.pmed.1001429
Abstract:
Influenza A H5N1 Clade 2.3.4 Virus with a Different Antiviral Susceptibility Profile Replaced Clade 1 Virus in Humans in Northern Vietnam
Mai T. Q. Le, Heiman F. L. Wertheim, Hien D. Nguyen, Walter Taylor, Phuong V. M. Hoang, Cuong D. Vuong, Hang L. K. Nguyen, Ha H. Nguyen, Thai Q. Nguyen, Trung V. Nguyen, Trang D. Van, Bich T. Ngoc, Thinh N. Bui, Binh G. Nguyen, Liem T. Nguyen, San T. Luong, Phuc H. Phan, Hung V. Pham, Tung Nguyen, Annette Fox, Cam V. Nguyen, Ha Q. Do, Martin Crusat, Jeremy Farrar, Hien T. Nguyen, Menno D. de Jong, Peter Horby
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0003339
Abstract: Background Prior to 2007, highly pathogenic avian influenza (HPAI) H5N1 viruses isolated from poultry and humans in Vietnam were consistently reported to be clade 1 viruses, susceptible to oseltamivir but resistant to amantadine. Here we describe the re-emergence of human HPAI H5N1 virus infections in Vietnam in 2007 and the characteristics of the isolated viruses. Methods and Findings Respiratory specimens from patients suspected to be infected with avian influenza in 2007 were screened by influenza and H5 subtype specific polymerase chain reaction. Isolated H5N1 strains were further characterized by genome sequencing and drug susceptibility testing. Eleven poultry outbreak isolates from 2007 were included in the sequence analysis. Eight patients, all of them from northern Vietnam, were diagnosed with H5N1 in 2007 and five of them died. Phylogenetic analysis of H5N1 viruses isolated from humans and poultry in 2007 showed that clade 2.3.4 H5N1 viruses replaced clade 1 viruses in northern Vietnam. Four human H5N1 strains had eight-fold reduced in-vitro susceptibility to oseltamivir as compared to clade 1 viruses. In two poultry isolates the I117V mutation was found in the neuraminidase gene, which is associated with reduced susceptibility to oseltamivir. No mutations in the M2 gene conferring amantadine resistance were found. Conclusion In 2007, H5N1 clade 2.3.4 viruses replaced clade 1 viruses in northern Vietnam and were susceptible to amantadine but showed reduced susceptibility to oseltamivir. Combination antiviral therapy with oseltamivir and amantadine for human cases in Vietnam is recommended.
Can mupirocin prevent methicillin-resistant Staphylococcus aureus infections?
Heiman FL Wertheim, Margreet C Vos
Critical Care , 2005, DOI: 10.1186/cc3720
Abstract: In this issue of Critical Care, AA Muller and colleagues present a study in which they assessed the efficacy of mupirocin nasal ointment in preventing methicillin-resistant Staphylococcus aureus (MRSA) infections in an intensive care unit (ICU) [1]. MRSA constitutes a special problem with regard to the prevention and treatment of infection. Studies show that MRSA carriers have a higher risk of nosocomial infection with this microorganism, and that those infected with MRSA have a greater morbidity and mortality than those infected with susceptible strains [2,3]. It is therefore important to keep the prevalence of MRSA carriage and MRSA infections low. Efforts to achieve this should be supported.Muller and colleagues performed a retrospective study in which they compared a 2-year MRSA control program with intranasal application of mupirocin, with a 2-year program in which mupirocin was not used. The MRSA control program consisted of screening for MRSA carriage at admission, and, in the event of MRSA carriage, hygienic measures to prevent cross-transmission were intensified. This study is clinically relevant, but the study design used is very susceptible to many biases and their results should therefore be interpreted with caution. Their findings, which suggest that intranasal mupirocin can prevent ICU-related MRSA infections, need confirmation in a well-designed clinical trial.Results from recent clinical trials that studied the efficacy of mupirocin nasal ointment in preventing methicillin-susceptible S. aureus (MSSA) infections can be extrapolated to MRSA infections. MSSA and MRSA are essentially the same microorganism, except that the latter is more difficult to treat with antibiotics. Several double-blind randomized placebo-controlled trials with mupirocin nasal ointment have been performed in both surgical and non-surgical patients, with S. aureus infection as the outcome measurement [4-7]. The results of these trials have been disappointing. So far, there is onl
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