Prevalence and implications of multiple-strain infections.

Infections frequently contain multiple strains (genotypes) of the same pathogen, yet they are still usually treated as uniform entities. In this Review, we discuss problems with inconsistent definition of the term "strain" and review the prevalence and implications of multiple-strain infections. Up to now, multiple-strain infections have been shown unambiguously in 51 human pathogens (and 21 non-human ones) and are likely to arise in most pathogen species. In human pathogens, multiple-strain infections usually reach considerable frequencies (median 11·3%, mean 21·7% of infections), which are certainly underestimated in many cases because of technical limitations of detection. For many diseases, the importance of multiple-strain infections is still unclear, but theoretical work and experimental results from animal models suggest a broad range of clinically relevant effects. Multiple-strain infections can affect host immune responses and our ability to prevent and treat infection efficiently. Competition and mutualism between strains change pathogen and disease dynamics and promote pathogen evolution. Co-infection enables gene transfer among strains. Taking multiple-strain infections into account will improve our understanding of host-pathogen interactions and disease dynamics, and will provide a basis for novel control approaches.

[1]  A. Hill,et al.  Altered peptide ligands narrow the repertoire of cellular immune responses by interfering with T-cell priming , 1999, Nature Medicine.

[2]  W. Bautsch,et al.  Macrorestriction analysis ofPseudomonas aeruginosa in colonized burn patients , 1994, European Journal of Clinical Microbiology and Infectious Diseases.

[3]  J. E. Hyde,et al.  Prevalence of Toxoplasma gondii in commercial meat products as monitored by polymerase chain reaction--food for thought? , 2002, International journal for parasitology.

[4]  J. Beadell,et al.  Phylogeography and Taxonomy of Trypanosoma brucei , 2011, PLoS neglected tropical diseases.

[5]  H. Al-Mohammed.  Genotypes of Giardia intestinalis clinical isolates of gastrointestinal symptomatic and asymptomatic Saudi children , 2011, Parasitology Research.

[6]  J. Sauver,et al.  Risk factors for otitis media and carriage of multiple strains of Haemophilus influenzae and Streptococcus pneumoniae. , 2000, Emerging infectious diseases.

[7]  A. Read,et al.  Dynamics of Multiple Infection and Within‐Host Competition in Genetically Diverse Malaria Infections , 2005, The American Naturalist.

[8]  A. Copas,et al.  Genotypic variation in Pneumocystis jirovecii isolates in Britain , 2005, Thorax.

[9]  C. Schmid,et al.  Hepatitis C virus genotype does not affect patient survival among renal transplant candidates , 1999 .

[10]  J. Sattabongkot,et al.  Genetic structures of geographically distinct Plasmodium vivax populations assessed by PCR/RFLP analysis of the merozoite surface protein 3beta gene. , 2006, Acta tropica.

[11]  C. Dye,et al.  Replication, differentiation, growth and the virulence of Trypanosoma brucei infections , 1995, Parasitology.

[12]  S. Tan,et al.  Detection and genotyping of human herpes simplex viruses in cutaneous lesions of erythema multiforme by nested PCR , 2003, Journal of medical virology.

[13]  Daijin Kim,et al.  High prevalence of HBV and HCV infection among intravenous drug users in Korea , 2008, Journal of medical virology.

[14]  C. B. Cropp,et al.  Common occurrence of concurrent infections by multiple dengue virus serotypes. , 1999, The American journal of tropical medicine and hygiene.

[15]  Sue J Lee,et al.  Simultaneous Infection with More than One Strain of Burkholderia pseudomallei Is Uncommon in Human Melioidosis , 2007, Journal of Clinical Microbiology.

[16]  L. Ranford-Cartwright,et al.  The epidemiology of multiple Plasmodium falciparum infections. 3. Genetic structure and dynamics of Plasmodium falciparum infections in the Kilombero region of Tanzania , 1999 .

[17]  G. Hardin,et al.  The Tragedy of the Commons , 1968, Green Planet Blues.

[18]  Thomas A. Smith,et al.  A recombinant blood-stage malaria vaccine reduces Plasmodium falciparum density and exerts selective pressure on parasite populations in a phase 1-2b trial in Papua New Guinea. , 2002, The Journal of infectious diseases.

[19]  W. J. Bean,et al.  Coinfection of wild ducks by influenza A viruses: distribution patterns and biological significance , 1997, Journal of virology.

[20]  M. Achtman,et al.  Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[21]  C. Clark,et al.  Terminology for Blastocystis subtypes--a consensus. , 2007, Trends in parasitology.

[22]  Sarah Rowland-Jones,et al.  Cytotoxic T-cell activity antagonized by naturally occurring HIV-1 Gag variants , 1994, Nature.

[23]  J. Kleibeuker,et al.  The importance of vacA, cagA, and iceA genotypes of Helicobacter pylori infection in peptic ulcer disease and gastroesophageal reflux disease , 2001, American Journal of Gastroenterology.

[24]  V. Jamonneau,et al.  Genetic variability within Trypanosoma brucei gambiense: evidence for the circulation of different genotypes in human African trypanosomiasis patients in Côte d'Ivoire. , 2002, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[25]  I. Pavlik,et al.  Mycobacterium avium subsp. avium distribution studied in a naturally infected hen flock and in the environment by culture, serotyping and IS901 RFLP methods. , 2008, Veterinary microbiology.

[26]  N. Wellinghausen,et al.  Evidence of Coinfection with Distinct Strains of Burkholderia multivorans in a Cystic Fibrosis Patient , 2006, Infection.

[27]  C. F. von Reyn,et al.  Genetic diversity among strains of Mycobacterium avium causing monoclonal and polyclonal bacteremia in patients with AIDS. , 1993, The Journal of infectious diseases.

[28]  D. Minchella,et al.  Distribution of schistosome genetic diversity within molluscan intermediate hosts , 1995, Parasitology.

[29]  J. Mathews,et al.  Carriage of multiple ribotypes of non-encapsulated Haemophilus influenzae in Aboriginal infants with otitis media , 1996, Epidemiology and Infection.

[30]  C. Hannoun,et al.  Genotype mixtures of hepatitis B virus in patients treated with interferon. , 2002, The Journal of infectious diseases.

[31]  T. Giraud,et al.  Within-host competitive exclusion among species of the anther smut pathogen , 2009, BMC Ecology.

[32]  R. Venezia,et al.  Bactericidal substance produced by Haemophilus influenzae b. , 1975, Canadian journal of microbiology.

[33]  J. Jordens,et al.  Molecular epidemiology of a multiple strain outbreak of methicillin-resistant Staphylococcus aureus amongst patients and staff. , 1995, The Journal of hospital infection.

[34]  A. Zuckerman.  Effect of hepatitis B virus mutants on efficacy of vaccination , 2000, The Lancet.

[35]  P. Kwok,et al.  Methods for genotyping single nucleotide polymorphisms. , 2003, Annual review of genomics and human genetics.

[36]  M Tanner,et al.  Age dependence of the multiplicity of Plasmodium falciparum infections and of other malariological indices in an area of high endemicity. , 1999, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[37]  S. Kim,et al.  Rapid Identification of Human Adenovirus Types 3 and 7 from Respiratory Specimens via Multiplex Type-Specific PCR , 2005, Journal of Clinical Microbiology.

[38]  T. Nishizawa,et al.  High prevalence of dual or triple infection of hepatitis B, C, and delta viruses among patients with chronic liver disease in Mongolia , 2005, Journal of medical virology.

[39]  F. H. Rodd,et al.  Evaluation of the Rate of Evolution in Natural Populations of Guppies (Poecilia reticulata) , 1997, Science.

[40]  W. Peetermans,et al.  Polyclonal staphylococcus endocarditis. , 1997, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[41]  Dieter Ebert,et al.  Challenging the trade-off model for the evolution of virulence: is virulence management feasible? , 2003, Trends in microbiology.

[42]  O. Balmer,et al.  New fluorescence markers to distinguish co-infecting Trypanosoma brucei strains in experimental multiple infections. , 2006, Acta tropica.

[43]  Thomas C Victor,et al.  Patients with active tuberculosis often have different strains in the same sputum specimen. , 2004, American journal of respiratory and critical care medicine.

[44]  Paul E. Turner,et al.  Prisoner's dilemma in an RNA virus , 1999, Nature.

[45]  J. Bartlett.  Dual HIV-1 infection associated with rapid disease progression , 2004 .

[46]  Roberts Rg,et al.  Bactericidal substance produced by Haemophilus influenzae b. , 1975 .

[47]  M. Tibayrenc,et al.  Microsatellite analysis of Toxoplasma gondii shows considerable polymorphism structured into two main clonal groups. , 2002, International journal for parasitology.

[48]  J. Zenilman,et al.  Genetic Typing of the Porin Protein of Neisseria gonorrhoeae from Clinical Noncultured Samples for Strain Characterization and Identification of Mixed Gonococcal Infections , 2005, Journal of Clinical Microbiology.

[49]  F. Bistoni,et al.  Glucuronoxylomannan exhibits potent immunosuppressive properties. , 2006, FEMS yeast research.

[50]  M. Galinski,et al.  Characterization and application of multiple genetic markers for Plasmodium malariae , 2006, Parasitology.

[51]  P. Ringwald,et al.  Molecular epidemiology of malaria in Cameroon. XXIV. Trends of in vitro antimalarial drug responses in Yaounde, Cameroon. , 2007, The American journal of tropical medicine and hygiene.

[52]  B. Söderquist,et al.  Genetic homogeneity/heterogeneity of Propionibacterium acnes isolated from patients during cardiothoracic reoperation. , 2007, Anaerobe.

[53]  P. Upcroft,et al.  Two Distinct Varieties of Giardia in a Mixed Infection from a Single Human Patient , 1994, The Journal of eukaryotic microbiology.

[54]  G. Hardin.  The competitive exclusion principle. , 1960, Science.

[55]  R. Holt.  Predation, apparent competition, and the structure of prey communities. , 1977, Theoretical population biology.

[56]  D. Kwiatkowski,et al.  Association of malaria parasite population structure, HLA, and immunological antagonism. , 1998, Science.

[57]  C. Rogier,et al.  Age-dependent carriage of multiple Plasmodium falciparum merozoite surface antigen-2 alleles in asymptomatic malaria infections. , 1995, American Journal of Tropical Medicine and Hygiene.

[58]  L. Engstrand,et al.  Occurence of resistance mutation and clonal expansion in Helicobacter pylori multiple-strain infection: a potential risk in clarithromycin-based therapy. , 1999, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[59]  M. Begon,et al.  Ecology: Individuals, Populations and Communities , 1986 .

[60]  Andrew Read,et al.  Exposing malaria in-host diversity and estimating population diversity by capture-recapture using massively parallel pyrosequencing , 2010, Proceedings of the National Academy of Sciences.

[61]  L. Chao,et al.  Structured habitats and the evolution of anticompetitor toxins in bacteria. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[62]  G. Boiteau,et al.  J. Virol. Methods , 1996, Journal of Virological Methods.

[63]  U. Fagundes-neto,et al.  Evaluation of Multiplex PCRs for Diagnosis of Infection with Diarrheagenic Escherichia coli and Shigella spp , 2004, Journal of Clinical Microbiology.

[64]  L. Vanhamme,et al.  A VSG Expression Site–Associated Gene Confers Resistance to Human Serum in Trypanosoma rhodesiense , 1998, Cell.

[65]  S. Stearns.  Evolution in Health and Disease , 2008 .

[66]  K. Leder,et al.  Illness in travelers visiting friends and relatives: a review of the GeoSentinel Surveillance Network. , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[67]  A. Caccone,et al.  Multiple-strain infections of Trypanosoma brucei across Africa. , 2008, Acta tropica.

[68]  F. X. Bosch,et al.  Epidemiologic classification of human papillomavirus types associated with cervical cancer. , 2003, The New England journal of medicine.

[69]  C. Raccurt,et al.  Similar genotypes of Pneumocystis jirovecii in different forms of Pneumocystis infection. , 2004, Microbiology.

[70]  S. Tzipori,et al.  Identification of genotypically mixed Cryptosporidium parvum populations in humans and calves. , 2003, Molecular and biochemical parasitology.

[71]  J. T. Crawford,et al.  Simultaneous infection with multiple strains of Mycobacterium tuberculosis. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[72]  J. Carr,et al.  Detection of HIV-1 subtypes, recombinants, and dual infections in east Africa by a multi-region hybridization assay , 2002, AIDS.

[73]  F. Pratlong,et al.  Short report: Treatment failure due to mixed infection by different strains of the parasite Leishmania infantum. , 2004, The American journal of tropical medicine and hygiene.

[74]  G. Srivastava,et al.  Coinfection of multiple strains of Epstein-Barr virus in immunocompetent normal individuals: reassessment of the viral carrier state. , 2000, Blood.

[75]  D. Gray,et al.  The Role of Immune‐Mediated Apparent Competition in Genetically Diverse Malaria Infections , 2006, The American Naturalist.

[76]  K. Toriyama,et al.  Genotypes of hepatitis B virus among voluntary blood donors in northern Thailand. , 2006, Hepatology research : the official journal of the Japan Society of Hepatology.

[77]  J. Adams,et al.  Plasmodium vivax: favored gene frequencies of the merozoite surface protein-1 and the multiplicity of infection in a malaria endemic region. , 1996, Experimental parasitology.

[78]  A. R. Noriega,et al.  Evidence of exogenous reinfection and mixed infection with more than one strain of Mycobacterium tuberculosis among Spanish HIV-infected inmates. , 1999, AIDS.

[79]  D. Wareing,et al.  Coinfection with Campylobacter species: an epidemiological problem? , 2001, Journal of applied microbiology.

[80]  P. Corraini,et al.  Prevalence and distribution of serotype-specific genotypes of Aggregatibacter actinomycetemcomitans in chronic periodontitis Brazilian subjects. , 2010, Archives of oral biology.

[81]  A. Craig,et al.  Limited spatial clustering of individual Plasmodium falciparum alleles in field isolates from coastal Kenya. , 1997, The American journal of tropical medicine and hygiene.

[82]  S. Fukushima,et al.  Isolation, partial purification and preliminary characterization of a bacteriocin from Streptococcus mutans Rm-10 , 1983, Antonie van Leeuwenhoek.

[83]  M. Begon,et al.  Ecology: Individuals, Populations and Communities , 1986 .

[84]  M. Burton,et al.  Chlamydia trachomatis ompA Variants in Trachoma: What Do They Tell Us? , 2008, PLoS neglected tropical diseases.

[85]  M. Begon,et al.  Ecology: Individuals, Populations and Communities, 3rd edn. , 1997 .

[86]  P. Prodöhl,et al.  Evidence for multiple mitochondrial lineages of Fasciola hepatica (liver fluke) within infrapopulations from cattle and sheep , 2007, Parasitology Research.

[87]  Jonathan Dushoff,et al.  Ecology and evolution of the flu , 2002 .

[88]  S. West,et al.  Determinants of trachoma endemicity using Chlamydia trachomatis ompA DNA sequencing. , 2001, Microbes and infection.

[89]  E. Calderón,et al.  Pneumocystis jiroveci genotypes in the Spanish population. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[90]  M Tanner,et al.  The epidemiology of multiple Plasmodium falciparum infections. 11. Premunition in Plasmodium falciparum infection : Insights from the epidemiology of multiple infections , 1999 .

[91]  D. Sim,et al.  WITHIN‐HOST COMPETITION IN GENETICALLY DIVERSE MALARIA INFECTIONS: PARASITE VIRULENCE AND COMPETITIVE SUCCESS , 2006, Evolution; international journal of organic evolution.

[92]  Steven A. Frank,et al.  Models of Parasite Virulence , 1996, The Quarterly Review of Biology.

[93]  P. V. van Helden,et al.  Reinfection and mixed infection cause changing Mycobacterium tuberculosis drug-resistance patterns. , 2005, American journal of respiratory and critical care medicine.

[94]  H. Agut,et al.  Length variability of telomeric repeat sequences of human herpesvirus 6 DNA. , 2009, Journal of virological methods.

[95]  J. H. I. Huis in't Veld,et al.  Overview of gut flora and probiotics. , 1998, International journal of food microbiology.

[96]  D. Dykhuizen,et al.  Four Clones of Borrelia burgdorferiSensu Stricto Cause Invasive Infection in Humans , 1999, Infection and Immunity.

[97]  J. Utzinger,et al.  Molecular epidemiology of human Blastocystis in a village in Yunnan province, China. , 2007, Parasitology international.

[98]  Jianjun Li,et al.  Co-infection with two different Campylobacter jejuni strains in a patient with the Guillain-Barré syndrome. , 2006, Microbes and infection.

[99]  F. Cox,et al.  Concomitant infections, parasites and immune responses , 2001, Parasitology.

[100]  T. Anderson,et al.  Mitochondrial DNA and Ascaris microepidemiology: the composition of parasite populations from individual hosts, families and villages , 1995, Parasitology.

[101]  K. Rudi,et al.  Co-Infection Dynamics of a Major Food-Borne Zoonotic Pathogen in Chicken , 2007, PLoS pathogens.

[102]  C. Rogier,et al.  No influence of age on infection complexity and allelic distribution in Plasmodium falciparum infections in Ndiop, a Senegalese village with seasonal, mesoendemic malaria. , 1998, The American journal of tropical medicine and hygiene.

[103]  A. Varin,et al.  Mixed cytomegalovirus glycoprotein B genotypes in immunocompromised patients. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[104]  J. Walboomers,et al.  Distribution of 37 mucosotropic HPV types in women with cytologically normal cervical smears: The age‐related patterns for high‐risk and low‐risk types , 2000, International journal of cancer.

[105]  A. Solari,et al.  Trypanosoma cruzi isolates from Chile are heterogeneous and composed of mixed populations when characterized by schizodeme and Southern analyses , 2004, Parasitology.

[106]  S. Obaro,et al.  Carriage of pneumococci after pneumococcal vaccination , 1996, The Lancet.

[107]  A. Read,et al.  The Ecology of Genetically Diverse Infections , 2001, Science.

[108]  Axel Meyer,et al.  Molecular systematics (2nd edn): edited by David M. Hillis, Craig Moritz and Barbara K. Mable Sinauer Associates, 1996. $49.95 pbk (655 pages) ISBN 0 87893 282 8 , 1996 .

[109]  E. Mendes,et al.  Distribution of vacA genotypes in Helicobacter pylori strains isolated from Brazilian adult patients with gastritis, duodenal ulcer or gastric carcinoma. , 2002, FEMS immunology and medical microbiology.

[110]  C. Lacroix,et al.  Construction and characterization of Enterococcus faecalis CG110/gfp/pRE25*, a tool for monitoring horizontal gene transfer in complex microbial ecosystems. , 2010, FEMS microbiology letters.

[111]  Shaw-Hwa Lo,et al.  The clonality of Staphylococcus aureus nasal carriage. , 2005, The Journal of infectious diseases.

[112]  R. Price,et al.  Genetic analysis of Plasmodium falciparum infections on the north-western border of Thailand. , 1999, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[113]  Riccardo Pansini,et al.  Virulence and competitive ability in genetically diverse malaria infections. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[114]  A. Casadevall,et al.  Molecular Epidemiology of Clinical Cryptococcus neoformans Strains from India , 2005, Journal of Clinical Microbiology.

[115]  J. Lines,et al.  Population structure of Plasmodium falciparum in villages with different malaria endemicity in east Africa. , 1997, The American journal of tropical medicine and hygiene.

[116]  M. Walshaw,et al.  Superinfection with a transmissible strain of Pseudomonas aeruginosa in adults with cystic fibrosis chronically colonised by P aeruginosa , 2001, The Lancet.

[117]  M. Dodd,et al.  Evidence for transmission of Pseudomonas cepacia by social contact in cystic fibrosis , 1993, The Lancet.

[118]  D. Dykhuizen,et al.  Genetic diversity of ospC in a local population of Borrelia burgdorferi sensu stricto. , 1999, Genetics.

[119]  C. Beard,et al.  Genetic variation in Pneumocystis carinii isolates from different geographic regions: implications for transmission. , 2000, Emerging infectious diseases.

[120]  Akira Sasaki,et al.  Why are dengue virus serotypes so distantly related? Enhancement and limiting serotype similarity between dengue virus strains , 2003, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[121]  F. Ayala,et al.  Clonal population structure and genetic diversity of Candida albicans in AIDS patients from Abidjan (Côte d'Ivoire). , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[122]  D. Carter,et al.  Phenotypic Switching and Genetic Diversity ofCryptococcus neoformans , 2001, Journal of Clinical Microbiology.

[123]  S. Faruque,et al.  Epidemiology, Genetics, and Ecology of ToxigenicVibrio cholerae , 1998, Microbiology and Molecular Biology Reviews.

[124]  N. Chilton,et al.  Multilocus enzyme electrophoresis: a valuable technique for providing answers to problems in parasite systematics. , 1999, International journal for parasitology.

[125]  F. Vargas,et al.  Selection of Trypanosoma cruzi clonal genotypes (clonet 20 and 39) isolated from Bolivian triatomines following subculture in liquid medium. , 2000, Memorias do Instituto Oswaldo Cruz.

[126]  A. Sette,et al.  Natural variants of cytotoxic epitopes are T-cell receptor antagonists for antiviral cytotoxic T cells , 1994, Nature.

[127]  S. Ellner,et al.  Rapid evolution and the convergence of ecological and evolutionary time , 2005 .

[128]  R. Anderson.  The pandemic of antibiotic resistance , 1999, Nature Medicine.

[129]  L. T. Figueiredo,et al.  Human cytomegalovirus glycoprotein B genotypes in Brazilian mothers and their congenitally infected infants , 2007, Journal of medical virology.

[130]  K. Mølbak,et al.  Characterisation of rotavirus strains among hospitalised and non-hospitalised children in Guinea-Bissau, 2002 A high frequency of mixed infections with serotype G8. , 2005, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[131]  R. May,et al.  The maintenance of strain structure in populations of recombining infectious agents , 1996, Nature Medicine.

[132]  S. Salmaso,et al.  Simultaneous infection with three different S. enteritidis strains in a nursing home resident , 1993, European Journal of Epidemiology.

[133]  M. Woolhouse,et al.  On the distribution of schistosome infections among host snails. , 1990, International journal for parasitology.

[134]  R. Stephens,et al.  Identification of individual genotypes of Chlamydia trachomatis from experimentally mixed serovars and mixed infections among trachoma patients , 1994, Journal of clinical microbiology.

[135]  S. Kabra,et al.  Concurrent infections by all four dengue virus serotypes during an outbreak of dengue in 2006 in Delhi, India , 2008, Virology Journal.

[136]  F. Lewis,et al.  DISTRIBUTION OF SCHISTOSOME INFECTIONS IN MOLLUSCAN HOSTS AT DIFFERENT LEVELS OF PARASITE PREVALENCE , 2002, The Journal of parasitology.

[137]  M. Chou,et al.  Study of an outbreak of Enterobacter cloacae sepsis in a neonatal intensive care unit: the application of epidemiologic chromosome profiling by pulsed-field gel electrophoresis. , 2002, American journal of infection control.

[138]  S. Stearns,et al.  Intraspecific competition between co-infecting parasite strains enhances host survival in African trypanosomes. , 2009, Ecology.

[139]  M. Alpers,et al.  Plasmodium falciparum: malaria morbidity is associated with specific merozoite surface antigen 2 genotypes. , 1995, Experimental parasitology.

[140]  Yi‐Hsiang Huang,et al.  Mixed genotypes infection with hepatitis D virus , 1999, Journal of medical virology.

[141]  D. Cooper,et al.  Coinfection with A- and B-type Epstein-Barr virus in human immunodeficiency virus-positive subjects. , 1990, The Journal of infectious diseases.

[142]  A. MacLeod,et al.  A high level of mixed Trypanosoma brucei infections in tsetse flies detected by three hypervariable minisatellites. , 1999, Molecular and biochemical parasitology.

[143]  K. O'Brien,et al.  Immunoblot Method To Detect Streptococcus pneumoniae and Identify Multiple Serotypes from Nasopharyngeal Secretions , 2004, Journal of Clinical Microbiology.

[144]  N. Ferguson,et al.  Chaos, persistence, and evolution of strain structure in antigenically diverse infectious agents. , 1998, Science.

[145]  R. Carter,et al.  Real-time quantitative PCR for analysis of genetically mixed infections of malaria parasites: technique validation and applications. , 2003, Molecular and biochemical parasitology.

[146]  J. Kleibeuker,et al.  The importance of vacA, cagA, and iceA genotypes of Helicobacter pylori infection in peptic ulcer disease and gastroesophageal reflux disease , 2001 .

[147]  L. Resnick,et al.  Coinfection with multiple strains of the Epstein-Barr virus in human immunodeficiency virus-associated hairy leukoplakia. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[148]  Sam P. Brown,et al.  Does multiple infection select for raised virulence? , 2002, Trends in microbiology.

[149]  Rolf M. Zinkernagel,et al.  Original antigenic sin impairs cytotoxic T lymphocyte responses to viruses bearing variant epitopes , 1998, Nature.

[150]  T. Nishizawa,et al.  Molecular investigation of hepatitis E virus infection in patients with acute hepatitis in Kathmandu, Nepal , 2003, Journal of medical virology.