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Bill Hanage

Harvard School of Public Health

Associate Professor

Department of Epidemiology

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Dr. Hanage employs a mix of theoretical and laboratory work to research the evolution and epidemiology of infectious disease. After his PhD, he engaged in post doctoral study at the University of Oxford and Imperial College London, before being awarded a Royal Society University Research Fellowship. Prior to joining CCDD he was a Reader in the department of Infectious Disease Epidemiology at Imperial College London.

Dr. Hanage has worked extensively developing multilocus sequence typing (MLST; www.mlst.net) and analysis (MLSA) for the study of bacterial pathogens and species, as well as means of analyzing data developed using this method. Along with his more theoretical projects he has worked on both bacterial (Neisseria, Streptococci) and viral pathogens (HIV-1, H1N1 influenza). He is particularly interested in using an evolutionary framework such as methods derived from population genetics to inform epidemiology. He has acted as an advisor to Glaxo SmithKline and the World Health Organisation.

The Distribution of Pairwise Genetic Distances: A Tool for Investigating Disease Transmission.

Worby CJ, Chang HH, Hanage WP, Lipsitch M.

Whole genome sequencing of pathogens has recently been used to investigate disease outbreaks, and is likely to play a growing role in real-time epidemiological studies. Methods to analyze high-resolution genomic data in this context are still lacking... (more »).

Genetics.   2014 Oct.

Antibiotics in agriculture and the risk to human health: how worried should we be?

Chang Q, Wang W, Regev-Yochay G, Lipsitch M, Hanage WP.

The use of antibiotics in agriculture is routinely described as a major contributor to the clinical problem of resistant disease in human medicine. While a link is plausible, there are no data conclusively showing the magnitude of the threat emerging... (more »).

Evolutionary Applications   2014 Sep.

Heterogeneity in the frequency and characteristics of homologous recombination in pneumococcal evolution.

Mostowy R, Croucher NJ, Hanage WP, Harris SR, Bentley S, Fraser C.

The bacterium Streptococcus pneumoniae (pneumococcus) is one of the most important human bacterial pathogens, and a leading cause of morbidity and mortality worldwide. The pneumococcus is also known for undergoing extensive homologous recombination v... (more »).

PLoS Genet.   2014 May. 10 (5): e1004300  

Within-host bacterial diversity hinders accurate reconstruction of transmission networks from genomic distance data.

Worby CJ, Lipsitch M, Hanage WP.

The prospect of using whole genome sequence data to investigate bacterial disease outbreaks has been keenly anticipated in many quarters, and the large-scale collection and sequencing of isolates from cases is becoming increasingly feasible. While se... (more »).

PLoS Comput Biol.   2014 Mar. 10 (3): e1003549  

Genomic epidemiology of Neisseria gonorrhoeae with reduced susceptibility to cefixime in the USA: a retrospective observational study.

Grad YH, Kirkcaldy RD, Trees D, Dordel J, Harris SR, Goldstein E, Weinstock H, Parkhill J, Hanage WP, Bentley S, Lipsitch M.

The emergence of Neisseria gonorrhoeae with decreased susceptibility to extended spectrum cephalosporins raises the prospect of untreatable gonorrhoea. In the absence of new treatments, efforts to slow the increasing incidence of resistant gonococcus... (more »).

Lancet Infect Dis.   2014 Jan.

Evolutionary dynamics of Vibrio cholerae O1 following a single-source introduction to Haiti.

Katz LS, Petkau A, Beaulaurier J, Tyler S, Antonova ES, Turnsek MA, Guo Y, Wang S, Paxinos EE, Orata F, Gladney LM, Stroika S, Folster JP, Rowe L, Freeman MM, Knox N, Frace M, Boncy J, Graham M, Hammer BK, Boucher Y, Bashir A, Hanage WP, Van Domselaar G, Tarr CL.

Prior to the epidemic that emerged in Haiti in October of 2010, cholera had not been documented in this country. After its introduction, a strain of Vibrio cholerae O1 spread rapidly throughout Haiti, where it caused over 600,000 cases of disease and... (more »).

MBio.   2013 Jul. 4 (4): e00398-13.  

Historical zoonoses and other changes in host tropism of Staphylococcus aureus, identified by phylogenetic analysis of a population dataset.

Shepheard MA, Fleming VM, Connor TR, Corander J, Feil EJ, Fraser C, Hanage WP.

Staphylococcus aureus exhibits tropisms to many distinct animal hosts. While spillover events can occur wherever there is an interface between host species, changes in host tropism only occur with the establishment of sustained transmission in the ne... (more »).

PLoS One   2013 May. 8 (5): e62369.  

Research areas: Staphylococcus aureus

Horizontal gene transfer and the evolution of bacterial and archaeal population structure.

Polz MF, Alm EJ, Hanage WP.

Many bacterial and archaeal lineages have a history of extensive and ongoing horizontal gene transfer and loss, as evidenced by the large differences in genome content even among otherwise closely related isolates. How ecologically cohesive populatio... (more »).

Trends Genet.   2013 Mar. 29 (3): 170-5.  

Bacterial genomes in epidemiology--present and future.

Croucher NJ, Harris SR, Grad YH, Hanage WP.

Sequence data are well established in the reconstruction of the phylogenetic and demographic scenarios that have given rise to outbreaks of viral pathogens. ... (more »).

Philos Trans R Soc Lond B Biol Sci.   2013 Mar.

Research areas: Genomics

Inference on population histories by approximating infinite alleles diffusion.

Siren J, Hanage WP, Corander J

Reconstruction of the past is an important task of evolutionary biology. It takes place at different points in a hierarchy of molecular variation, including genes, individuals, populations, and species. Statistical inference about population historie... (more »).

Mol Biol Evol   2013 Feb.

Comparative genomics of recent shiga toxin-producing Escherichia coli O104:H4: short-term evolution of an emerging pathogen.

Grad YH, Godfrey P, Cerquiera GC, Mariani-Kurkdijian P, Gouli M, Bingin E, Shea TP, Haas BJ, Griggs A, Young S, Zeng Q, Lipsitch M, Waldor MK, Weill FX, Wortman JR, Hanage WP.

The large outbreak of diarrhea and hemolytic uremic syndrome (HUS) caused by Shiga toxin-producing Escherichia coli O104:H4 in Europe from May to July 2011 highlighted the potential of a rarely identified E. coli serogro... (more »).

mBio   2013 Jan. 4 (1): e00452-12  

Reply to Guy et al.: Support for a bottleneck in the 2011 Escherichia coli O104:H4 outbreak in Germany.

Grad YH, Lipsitch M, Griggs AD, Haas BJ, Shea TP, McCowan C, Montmayeur A, FitzGerald M, Wortman JR, Krogfelt KA, Bingen E, Weill FX, Tietze E, Flieger A, Lander ES, Nusbaum C, Birren BW, Hung DT, Hanage WP.

In our paper (1), we analyzed isolates from the Escherichia coli O104:H4 outbreaks in Germany and France in May to July 2011. We concluded that, although the German outbreak was larger, the German isolates represent a clade within the greater diversi... (more »).

Proc Natl Acad Sci U S A.   2012 Dec. 109 (52): E3629-30  

Research areas: Escherichia coli

Population subdivision and the detection of recombination in non-typable Haemophilus influenza

Connor TR, Corander J, Hanage B

The disparity in diversity between unencapsulated (Non Typable, NT) and encapsulated, serotypable Haemophilus influenzae (Hi) has been recognised for some time. It has previously been suggested that the wider diversity evidenced within NT Hi compared... (more »).

Microbiology - Epub ahead of print   2012 Sep.

Research areas: influenza

Nontypeable pneumococcal isolates among navajo and white mountain apache communities: are these really a cause of invasive disease?

Scott JR, Hinds J, Gould KA, Millar EV, Reid R, Santosham M, O'Brien KL, Hanage WP

Pneumococci could evade pneumococcal conjugate vaccines (PCV) by modifying, mutating, or deleting vaccine-serotype capsule genes or by downregulating capsule production. We sought to assess whether pneumococci that are nontypeable (NT) by the Quellun... (more »).

J Infect Dis   2012 Jun. 206 (1): 73-80  

Research areas: Pneumococcal Disease

Restricted gene flow among hospital subpopulations of Enterococcus faecium

Willems RJ, Top J, van Schaik W, Leavis H, Bonten M, Sirén J, Hanage WP, Corander J

Enterococcus faecium has recently emerged as an important multiresistant nosocomial pathogen. Defining population structure in this species is required to provide insight into the existence, distribution, and dynamics of specific multiresistant or pa... (more »).

MBio   2012 Jun. 3 (4): e00151-12  

Variation at the capsule locus, cps, of mistyped and non-typable Streptococcus pneumoniae isolates

Salter SJ, Hinds J, Gould KA, Lambertsen L, Hanage WP, Antonio M, Turner P, Hermans PW, Bootsma HJ, O'Brien KL, Bentley SD

The capsule polysaccharide locus (cps) is the site of the capsule biosynthesis gene cluster in encapsulated Streptococcus pneumoniae. A set of pneumococcal samples and non-pneumococcal streptococci from Denmark, the Gambia, the Netherlands, Thailand,... (more »).

Microbiology   2012 May. 158 (6): 1560-9  

Research areas: Pneumococcal Disease

Population structure in the Neisseria, and the biological significance of fuzzy species

Corander J, Connor TR, O'Dwyer CA, Kroll JS, Hanage WP

Phenotypic and genetic variation in bacteria can take bewilderingly complex forms even within a single genus. One of the most intriguing examples of this is the genus Neisseria, which comprises both pathogens and commensals colonizing a variety of bo... (more »).

J R Soc Interface   2012 May. 9 (71): 1208-15  

Pneumococcal carriage and antibiotic resistance in young children before 13-valent conjugate vaccine

Wroe PC, Lee GM, Finkelstein JA, Pelton SI, Hanage WP, Lipsitch M, Stevenson AE, Rifas-Shiman SL, Kleinman K, Dutta-Linn MM, Hinrichsen VL, Lakoma M, Huang SS

BACKGROUND: We sought to measure trends in Streptococcus pneumoniae (SP) carriage and antibiotic resistance in young children in Massachusetts communities after widespread adoption of heptavalent pneumococcal conjugate vaccine (PCV7) and before the i... (more »).

Pediatr Infect Dis J   2012 Feb. 31 (3): 249-54  

Research areas: Pneumococcal Disease

Pneumococcal sequence type replacement among American Indian children: a comparison of pre- and routine-PCV7 eras

Scott JR, Hanage WP, Lipsitch M, Millar EV, Moulton LH, Hinds J, Reid R, Santosham M, O'Brien KL

BACKGROUND: Multi-locus sequence typing (MLST) of pneumococcal isolates collected during an efficacy trial of the 7-valent pneumococcal conjugate vaccine (PCV7) among Navajo and White Mountain Apache children from 1998 to 2000 showed a non-differenti... (more »).

Vaccine   2012 Feb. 30 (13): 2376-81  

Research areas: Pneumococcal Disease

Genomic epidemiology of the Escherichia coli O104:H4 outbreaks in Europe, 2011

Grad Y, Lipsitch M, Feldgarden M, Arachchi HM, Cerqueira GC, FitzGerald M, Godfrey P, Haas BJ, Murphy C, Russ C, Sykes S, Walker BJ, Wortman JR, Young S, Zeng Q, Abouelleil A, Bochicchio J, Chauvin S, DeSmet T, Gujja S, McCowan C, Montmayeur A, Steelman S, Frimodt-Moller J, Petersen AM, Struve C, Krogfelt KA, Bingen E, Weill FX, Lander ES, Nusbaum C, Birren BW, Hung DT, Hanage WP.

The degree to which molecular epidemiology reveals information about the sources and transmission patterns of an outbreak depends on the resolution of the technology used and the samples studied. Isolates of Escherichia coli O104:H4 fr... (more »).

PNAS   2012 Jan. 109 (8): 3065-70  

Detection of recombination events in bacterial genomes from large population samples

Marttinen P, Hanage WP, Croucher NJ, Connor TR, Harris SR, Bentley SD, Corander J

Analysis of important human pathogen populations is currently under transition toward whole-genome sequencing of growing numbers of samples collected on a global scale. Since recombination in bacteria is often an important factor shaping their evolut... (more »).

Nucleic Acids Res   2011 Dec. 40 (1): e6  

Clonal replacement among 19A Streptococcus pneumoniae in Massachusetts, prior to 13 valent conjugate vaccination

Hanage WP, Bishop CJ, Lee GM, Lipsitch M, Stevenson A, Rifas-Shiman SL, Pelton SI, Huang SS, Finkelstein JA

As part of an ongoing study of the response of the Streptococcus pneumoniae population to conjugate vaccination, we applied multi-locus sequence typing (MLST) to 291 isolates sampled from nasopharyngeal carriage in Massachusetts children. We found 94... (more »).

Vaccine   2011 Oct. 29 (48): 8877-81  

Research areas: Pneumococcal Disease

Pneumococcal carriage and antibiotic resistance in young children prior to 13-valent conjugate vaccine

Wroe PC, Lee GM, Finkelstein JA, Pelton SI, Hanage WP, Lipsitch M, Stevenson AE, Rifas-Shiman SL, Kleinman K, Dutta-Linn MM, Hinrichsen VL, Lakoma M, Huang SS

Following the introduction of heptavalent pneumococcal conjugate vaccine (PCV7) in 2000, the rates of invasive pneumococcal disease (IPD) in U.S. children have decreased substantially.[1-5]  Rates of other childhood pneumococcal illnesses such a... (more »).

PIDJ, In Press Oct 2011   2011 Sep.

Population biology of Gram-positive pathogens: high-risk clones for dissemination of antibiotic resistance

Willems RJ, Hanage WP, Bessen DE, Feil EJ

Infections caused by multiresistant Gram-positive bacteria represent a major health burden in the community as well as in hospitalized patients. Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium are well-known pathogens of hospita... (more »).

FEMS Microbiol Rev   2011 Aug. 35 (5): 872-900  

Carried pneumococci in Massachusetts children: the contribution of clonal expansion and serotype switching

Hanage WP, Bishop CJ, Huang SS, Stevenson AE, Pelton SI, Lipsitch M, Finkelstein JA

BACKGROUND: Vaccination against 7 serotypes of Streptococcus pneumoniae has led to the near extinction of vaccine serotypes in both disease and asymptomatic carriage. In carriage, vaccine serotypes have been replaced by nonvaccine serotypes. METHODS:... (more »).

Pediatr Infect Dis J   2011 Mar. 30 (4): 302-308  

Research areas: Pneumococcal Disease

Serotype specific invasive capacity and persistent reduction in invasive pneumococcal disease

Yildirim I, Hanage WP, Lipsitch M, Shea KM, Stevenson A, Finkelstein J, Huang SS, Lee GM, Kleinman K, Pelton SI

Defining the propensity of Streptococcus pneumoniae (SP) serotypes to invade sterile body sites following nasopharyngeal (NP) acquisition has the potential to inform about how much invasive pneumococcal disease (IPD) may occur in a typical population... (more »).

Vaccine   2010 Nov. 29 (2): 283-8  

Research areas: Pneumococcal Disease

Re-remergence of the type 1 pilus among Streptococcus pneumoniae isolates in Massachusetts, USA

Regev-Yochay G, Hanage WP, Trzcinski K, Rifas-Shiman SL, Lee G, Bessolo A, Huang SS, Pelton SI, McAdam AJ, Finkelstein JA, Lipsitch M, Malley R

Pneumococcal type 1 pilus proteins have been proposed as potential vaccine candidates. Following conjugate pneumococcal vaccination, the prevalence of the pneumococcal type 1 pilus declined dramatically, a decline associated with the elimination of v... (more »).

Vaccine   2010 Jun. 28 (30): 4842-4846  

Research areas: Pneumococcal Disease

What is the mechanism for persistent coexistence of drug-susceptible and drug-resistant strains of Streptococcus pneumoniae?

Colijn C, Cohen T, Fraser C, Hanage W, Goldstein E, Givon-Lavi N, Dagan R, Lipsitch M.

The emergence and global impact of the novel influenza A(H1N1)v highlights the continuous threat to public health posed by a steady stream of new and unexpected infectious disease outbreaks in animals and humans. Once an emerging epidemic is detected... (more »).

JR Soc Interface   2010 May. 7 (47): 905-19  

Research areas: Pneumococcal Disease

HIV-1 transmitting couples have similar viral load set-points in Rakai, Uganda

Hollingsworth TD, Laeyendecker O, Shirreff G, Donnelly CA, Serwadda D, Wawer MJ, Kiwanuka N, Nalugoda F, Collinson-Streng A, Ssempijja V, Hanage WP, Quinn TC, Gray RH, Fraser C.

It has been hypothesized that HIV-1 viral load set-point is a surrogate measure of HIV-1 viral virulence, and that it may be subject to natural selection in the human host population. A key test of this hypothesis is whether viral load set-points are... (more »).

PLoS Pathog   2010 Apr. 6 (5): e1000876  

Evidence that pneumococcal serotype replacement in Massachusetts following conjugate vaccination is now complete

Hanage WP, Finkelstein JA, Huang SS, Pelton SI, Stevenson AE, Kleinman K, Hinrichsen VL, Fraser C.

Invasive pneumococcal disease (IPD) has been reduced in the US following conjugate vaccination (PCV7) targeting seven pneumococcal serotypes in 2000. However, increases in IPD due to other serotypes have been observed, in particular 19A. How much thi... (more »).

Epidemics   2010 Feb. 2 (2): 80-84  

Research areas: Pneumococcal Disease

Identifying currents in the gene pool for bacterial populations using an integrative approach

Tang J, Hanage WP, Fraser C, Corander J

The evolution of bacterial populations has recently become considerably better understood due to large-scale sequencing of population samples. It has become clear that DNA sequences from a multitude of genes, as well as a broad sample coverage of a t... (more »).

PLoS Computational Biology   2009 Jul. 5 (8): e1000455  

Pandemic potential of a strain of influenza A (H1N1): early findings

Fraser C, Donnelly CA, Cauchemez S, Hanage B, Van Kerkhove MD, Hollingsworth TD, Griffin J, Baggaley RF, Jenkins HE, Lyons EJ, Jombart T, Hinsley WR, Grassly NC, Balloux F, Ghani AC, Ferguson NM, Rambaut A, Pybus OG, Lopez-Gatell H, Apluche-Aranda CM, Chapela IB, Zavala EP, Guevara DM, Checchi F, Garcia E, Hugonnet S, Roth C..

A novel influenza A (H1N1) virus has spread rapidly across the globe. Judging its pandemic potential is difficult with limited data, but nevertheless essential to inform appropriate health responses. By analyzing the outbreak in Mexico, early data on... (more »).

Science   2009 Jun. 324 (5934): 1557 - 1561  

Research areas: Pandemic H1N1 influenza

Epidemiology and risk factors for Staphylococcus aureus colonization in children in the post-PCV7 era

Lee GM, Huang SS, Rifas-Shiman SL, Hinrichsen VL, Pelton SI, Kleinman K, Hanage WP, Lipsitch M, McAdam AJ, Finkelstein J...

BACKGROUND: The incidence of community-associated methicillin-resistant Staphylococcus aureus (MRSA) has risen dramatically in the U.S., particularly among children. Although Streptococcus pneumoniae colonization has been inversely associated with S.... (more »).

BMC Infectious Diseases   2009 Jun. 9 110   10.1186/1471-2334-9-110

Continued impact of pneumococcal conjugate vaccine on carriage in young children

Huang SS, Hinrichsen VL, Stevenson AE, Rifas-Shiman SL, Kleinman K, Pelton SI, Lipsitch M, Hanage WP, Lee G, Finkelstein J.

OBJECTIVES: The goals were to assess serial changes in Streptococcus pneumoniae serotypes and antibiotic resistance in young children and to evaluate whether risk factors for carriage have been altered by heptavalent pneumococcal conjugate vaccine (P... (more »).

Pediatrics   2009 Jun. 124 (1): e1-e11  

Research areas: Pneumococcal Disease

Pandemic potential of a strain of influenza A (H1N1): early findings

Fraser C, Donnelly CA, Cauchemez S, Hanage WP, Van Kerkhove MD, Hollingsworth TD, Griffin J, Baggaley RF, Jenkins HE, Lyons EJ, Jombart T, Hinsley WR, Grassly NC, Balloux F, Ghani AC, Ferguson NM, Rambaut A, Pybus OG, Lopez-Gatell H, Alpuche-Aranda CM, Chapela IB, Zavala EP, Guevara DM, Checchi F, Garcia E, Hugonnet S, Roth C

A novel influenza A (H1N1) virus has spread rapidly across the globe. Judging its pandemic potential is difficult with limited data, but nevertheless essential to inform appropriate health responses. By analyzing the outbreak in Mexico, early data on... (more »).

Science   2009 May. 324 (5934): 1557-61  

Research areas: influenza, Pandemic H1N1 influenza

Hyper-recombination, diversity, and antibiotic resistance in pneumococcus

Hanage WP, Fraser C, Tang J, Connor TR, Corander J

Streptococcus pneumoniae is a pathogen of global importance that frequently transfers genetic material between strains and on occasion across species boundaries. In an analysis of 1930 pneumococcal genotypes from six housekeeping genes and 94 genotyp... (more »).

Science   2009 May. 324 (5933): 1454-1457  

Research areas: Pneumococcal Disease

No coexistence for free: neutral null models for multistrain pathogens

Lipsitch M, Colijn C, Cohen T, Hanage WP, Fraser C.

In most pathogens, multiple strains are maintained within host populations. Quantifying the mechanisms underlying strain coexistence would aid public health planning and improve understanding of disease dynamics. We argue that mathematical models of ... (more »).

Epidemics   2009 Feb. 1 (1): 2-13   10.1016/j.epidem.2008.07.001

The bacterial species challenge: making sense of genetic and ecological diversity

Fraser C, Alm EJ, Polz MF, Spratt BG, Hanage WP.

The Bacteria and Archaea are the most genetically diverse superkingdoms of life, and techniques for exploring that diversity are only just becoming widespread. Taxonomists classify these organisms into species in much the same way as they classify eu... (more »).

Science   2009 Jan. 323 (5915): 741-6  

Methods for data analysis

Hanage WP, Aanensen DM.

Methods in Molecular Biology   2008 Dec. 551 287-304  

Assigning strains to bacterial species via the internet

Bishop CJ, Aanensen DM, Jordan GE, Kilian M, Hanage WP, Spratt BG.

BACKGROUND: Methods for assigning strains to bacterial species are cumbersome and no longer fit for purpose. The concatenated sequences of multiple house-keeping genes have been shown to be able to define and circumscribe bacterial species as sequenc... (more »).

BMC Biology   2008 Dec. 7 3  

Charles Darwin in modern epidemiology and public health – the celebration continues

Hanage WP

2009 was Darwin year; his familiar bearded face peered out from a great radiation of TV series, book covers, and even a feature film. The reasons for this were his bicentennial and the 150th anniversary of the publication of the Origin of Species. Bu... (more »).

J Epidemiol Community Health   2008 Dec.

Distribution of pneumococcal surface protein A families 1 and 2 among Streptococcus pneumoniae isolates from children in Finland who had acute otitis media or were nasopharyngeal carriers

Melin MM, Hollingshead SK, Briles DE, Hanage WP, Lahdenkari M, Kaijalainen T, Kilpi TM, Kayhty HM

PspA is a structurally variable surface protein important to the virulence of pneumococci. PspAs are serologically cross-reactive and exist as two major families. In this study, we determined the distribution of PspA families 1 and 2 among pneumococc... (more »).

Clin Vaccine Immunol   2008 Sep. 15 (10): 1555-63  

Research areas: Pneumococcal Disease

Bayesian modeling of recombination events in bacterial populations

Marttinen P, Baldwin A, Hanage WP, Dowson C, Mahenthiralingam E, Corander J

BACKGROUND: We consider the discovery of recombinant segments jointly with their origins within multilocus DNA sequences from bacteria representing heterogeneous populations of fairly closely related species. The currently available methods for recom... (more »).

BMC Bioinformatics   2008 Sep. 9 421  

Streptococcus pneumoniae contains 3 rlrA pilus variants that are clonally related

Moschioni M, Donati C, Muzzi A, Masignani V, Censini S, Hanage WP, Bishop CJ, Reis JN, Normark S, Henriques-Normark B, Covacci A, Rappuoli R, Barocchi MA.

BACKGROUND: Pilus components of Streptococcus pneumoniae encoded by rlrA were recently shown to elicit protection in an animal model of infection. Limited data are available on the prevalence of the rlrA operon in pneumococci; therefore, we investiga... (more »).

J Infect Dis   2008 Feb. 197 (6): 888-96  

Research areas: Pneumococcal Disease

Serotype-specific problems associated with pneumococcal conjugate vaccination

Hanage WP

A conjugate vaccine against seven of the 91 known pneumococcal serotypes was licensed in the USA in 2000 and has had profound effects on pneumococcal disease and ecology. Among these is the virtual disappearance of vaccine serotypes from carriage, an... (more »).

Future Microbiol.   2008 Jan. 3 (1): 23-30  

Research areas: Pneumococcal Disease

Variation in HIV-1 set-point viral load: epidemiological analysis and an evolutionary hypothesis

Fraser C, Hollingsworth TD, Chapman R, de Wolf F, Hanage WP

The natural course of HIV-1 infection is characterized by a high degree of heterogeneity in viral load, not just within patients over time, but also between patients, especially during the asymptomatic stage of infection. Asymptomatic, or set-point, ... (more »).

Proc Natl Acad Sci U S A   2007 Sep. 104 (44): 17441-6  

Emergence of 19A as virulent and multidrug resistant Pneumococcus in Massachusetts following universal immunization of infants with pneumococcal conjugate vaccine

Pelton SI, Huot H, Finkelstein JA, Bishop CJ, Hsu KK, Kellenberg J, Huang SS, Goldstein R, Hanage W

BACKGROUND: The long-term effects of selective pressure from conjugate pneumococcal vaccine on the serotype distribution and antimicrobial resistance of carriage and invasive isolates of Streptococcus pneumoniae are unknown. Early changes demonstrate... (more »).

Pediatr Infect Dis J   2007 May. 26 (6): 468-72  

Research areas: Pneumococcal Disease

Assessing the reliability of eBURST using simulated populations with known ancestry

Turner KM, Hanage WP, Fraser C, Connor TR

BACKGROUND: The program eBURST uses multilocus sequence typing data to divide bacterial populations into groups of closely related strains (clonal complexes), predicts the founding genotype of each group, and displays the patterns of recent evolution... (more »).

BMC Microbiol   2007 Mar. 7 30  

Diversity and antibiotic resistance among nonvaccine serotypes of Streptococcus pneumoniae carriage isolates in the post-heptavalent conjugate vaccine era

Hanage WP, Huang SS, Lipsitch M, Bishop CJ, Godoy D, Pelton SI, Goldstein R, Huot H, Finkelstein J.

BACKGROUND: In response to the selective pressure of pneumococcal conjugate vaccine, increased asymptomatic carriage of antibiotic-nonsusceptible nonvaccine serotypes (NVTs) has been observed. Possible mechanisms include de novo acquisition of resist... (more »).

Journal of Infectious Diseases   2007 Jan. 195 (3): 347-352  

Research areas: Pneumococcal Disease

Recombination and the nature of bacterial speciation

Fraser C, Hanage WP, Spratt BG

Genetic surveys reveal the diversity of bacteria and lead to the questioning of species concepts used to categorize bacteria. One difficulty in defining bacterial species arises from the high rates of recombination that results in the transfer of DNA... (more »).

Science   2006 Dec. 315 (5811): 476-80  

Modelling bacterial speciation

Hanage WP, Fraser C, Turner K, Spratt BG.

A central problem in understanding bacterial speciation is how clusters of closely related strains emerge and persist in the face of recombination. We use a neutral Fisher-Wright model in which genotypes, defined by the alleles at 140 house-keeping l... (more »).

Philos Trans R Soc Lond B Biol Sci   2006 Oct. 361 (1475): 2039-44  

Sequences, sequence clusters and bacterial species

Hanage B, Fraser C, Spratt BG

Whatever else they should share, strains of bacteria assigned to the same species should have house-keeping genes that are similar in sequence. Single gene sequences (or rRNA gene sequences) have very few informative sites to resolve the strains of c... (more »).

Philos Trans R Soc Lond B Biol Sci   2006 Oct. 361 (1475): 1917-27  

The important role of non-typeable Streptococcus pneumoniae international clones in acute conjunctivitis

Porat N, Greenberg D, Givon N, Shuval D, Ronit T, Orit S, Hanage WP, Dagan R

Journal of Infectious Diseases   2006 Aug. 194 689-696  

Research areas: Pneumococcal Disease

Modelling infectious disease - time to think outside the box?

Wiles S, Hanage WP, Frankel G, Robertson B

Models occupy an essential position in the study of infectious disease as a result of the ethical problems of exposing humans to potentially lethal agents. Deliberately induced infections in well-defined animal models provide much useful information ... (more »).

Nat Rev Microbiol   2006 Mar. 4 (4): 307-12  

The impact of homologous recombination on the generation of diversity in bacteria

Hanage WP, Fraser C, Spratt BG

The imprint of demographic and selective processes on bacterial population structure needs to be evaluated as deviation from the expectations of an appropriate null neutral model. We explore the impact of varying the population mutation and recombina... (more »).

Journal of Theoretical Biology   2006 Feb. 239 (2): 210  

A successful, diverse disease-associated lineage of nontypeable pneumococci that has lost the capsular biosynthesis locus

Hanage WP, Kaijalainen T, Saukkoriipi A, Rickcord J, Spratt BG

Streptococcus pneumoniae strains which fail to produce a polysaccharide capsule are commonly isolated from carriage and disease contexts. Here we use a multilocus approach to distinguish genuine nontypeable pneumococci from closely related nontypeabl... (more »).

Journal of Clinical Microbiology   2006 Feb. 44 (3): 743-9  

Research areas: Pneumococcal Disease

Low effective dispersal of asexual genotypes in heterogeneous landscapes by the endemic pathogen Penicillium marneffei

Fisher MC, Hanage WP, de Hoog S, Johnson E, Smith MD, White NJ, Vanittanakom N.

Long-distance dispersal in microbial eukaryotes has been shown to result in the establishment of populations on continental and global scales. Such “ubiquitous dispersal” has been claimed to be a general feature of microbial eukaryotes, h... (more »).

PLoS Pathogens   2005 Sep. 1 (2): e20  

Using multilocus sequence data to define the pneumococcus

Hanage WP, Kaijalainen T, Herva E, Saukkoriipi A, Syrjänen R, Spratt BG

We investigated the genetic relationships between serotypeable pneumococci and nonserotypeable presumptive pneumococci using multilocus sequence typing (MLST) and partial sequencing of the pneumolysin gene (ply). Among 121 nonserotypeable presumptive... (more »).

J Bacteriol   2005 Aug. 187 (17): 6223-30  

Research areas: Pneumococcal Disease

Fuzzy species among recombinogenic bacteria

Hanage B, Fraser C, Spratt B

BACKGROUND: It is a matter of ongoing debate whether a universal species concept is possible for bacteria. Indeed, it is not clear whether closely related isolates of bacteria typically form discrete genotypic clusters that can be assigned as species... (more »).

BMC Biol   2005 Feb. 3 6  

Neutral microepidemic evolution of bacterial pathogens

Fraser C, Hanage WP, Spratt BG

Understanding bacterial population genetics is vital for interpreting the response of bacterial populations to selection pressures such as antibiotic treatment or vaccines targeted at only a subset of strains. The evolution of transmissible bacteria ... (more »).

Proc Natl Acad Sci USA   2005 Jan. 102 (6): 1968-73  

Invasiveness of serotypes and clones of Streptococcus pneumoniae among children in Finland

Hanage WP, Kaijalainen TH, Syrjänen RK, Auranen K, Leinonen M, Makela PH, Spratt BG.

Streptococcus pneumoniae (the pneumococcus) causes diseases from otitis media to life-threatening invasive infection. The species is extremely antigenically and clonally diverse. We wished to determine odds ratios (ORs) for serotypes and clones of S.... (more »).

Infect Immun   2004 Dec. 73 (1): 431-5  

Research areas: Pneumococcal Disease

Displaying the relatedness among isolates of bacterial species -- the eBURST approach

Spratt BG, Hanage WP, Li B, Aanensen DM, Feil EJ

Determining the most appropriate way to represent the relationships between bacterial isolates is complicated by the differing rates of recombination within species. In many cases, a bifurcating tree can be positively misleading. The recently describ... (more »).

FEMS Microbiol Lett   2004 Nov. 241 (2): 129-34.  

eBURST: inferring patterns of evolutionary descent among clusters of related bacterial genotypes from multilocus sequence typing data

Feil EJ, Li BC, Aanensen DM, Hanage WP, Spratt BG...

The introduction of multilocus sequence typing (MLST) for the precise characterization of isolates of bacterial pathogens has had a marked impact on both routine epidemiological surveillance and microbial population biology. In both fields, a key pre... (more »).

J Bacteriol   2004 Feb. 186 (5): 1518-30  

Ability of pneumococcal serotypes and clones to cause acute otitis media: implications for the prevention of otitis media by conjugate vaccines

Hanage WP, Auranen K, Syrjanen R, Herva E, Makela PH, Kilpi T, Spratt BG

The relative abilities of pneumococcal serotypes and strains (clones) to cause acute otitis media (AOM) were investigated by comparing the serotypes and genotypes of pneumococci recovered from cases of AOM (n = 149) in children <2 years of age wit... (more »).

Infect Immun   2003 Dec. 72 (1): 76-81  

Research areas: Pneumococcal Disease

Stimulation of cytokine release and adhesion molecule expression by products of viridans streptococci

Hanage WP, Cohen J

The viridans streptococci (VS) are associated with the development of a rapidly fulminant shock syndrome in neutropenic patients. A panel of 52 VS strains isolated from the blood of neutropenic patients was used to demonstrate the ability of culture ... (more »).

J Infect Dis   2002 Jan. 185 (3): 357-67  

The relative contributions of recombination and point mutation to the diversification of bacterial clones

Spratt BG, Hanage WP, Feil EJ

Low levels of recombination in bacterial species have often been inferred from the presence of linkage disequilibrium between the alleles at different loci in the population. However, significant linkage disequilibrium is inevitable in organisms that... (more »).

Curr Opin Microbiol   2001 Sep. 4 (5): 602-6