Quellung reaction

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The Quellung reaction, also called the Neufeld reaction, is a biochemical reaction in which antibodies bind to the bacterial capsule of Streptococcus pneumoniae, Klebsiella pneumoniae, Neisseria meningitidis, Haemophilus influenzae,[1] Escherichia coli, and Salmonella. The antibody reaction allows these species to be visualized under a microscope. If the reaction is positive, the capsule becomes opaque and appears to enlarge.

Photomicrograph of Streptococcus pneumoniae bacteria revealing capsular swelling using the Neufeld-Quellung test. Notice the two Streptococci at the top of the photo that appear to have no capsule.

Quellung is the German word for "swelling" and describes the microscopic appearance of pneumococcal or other bacterial capsules after their polysaccharide antigen has combined with a specific antibody. The antibody usually comes from a bit of serum taken from an immunized laboratory animal. As a result of this combination, and precipitation of the large, complex molecule formed, the capsule appears to swell, because of increased surface tension, and its outlines become clearly demarcated.

The pneumococcal Quellung reaction was first described in 1902 by the scientist Fred Neufeld, and applied only to Streptococcus pneumoniae, both as microscopic capsular swelling and macroscopic agglutination (clumping visible with the naked eye).[2] It was initially an intellectual curiosity more than anything else, and could distinguish only the three pneumococcal serotypes known at that time. However, it acquired an important practical use with the advent of serum therapy to treat certain types of pneumococcal pneumonia in the 1920s because selection of the proper antiserum to treat an individual patient required correct identification of the infecting pneumococcal serotype, and the Quellung reaction was the only method available to do this. Dr. Albert Sabin made modifications to Neufeld's technique so that it could be done more rapidly,[3] and other scientists expanded the technique to identify 29 additional serotypes.[4]

Application of Neufeld’s discoveries to other important areas of research came when Fred Griffith showed that pneumococci could transfer information to transform one serotype into another.[5] Oswald Avery, Colin MacLeod, and Maclyn McCarty later showed that the transforming factor was deoxyribonucleic acid, or DNA.[6]

Serum therapy for infectious diseases was displaced by antibiotics in the 1940s, but identification of specific serotypes remained important as the understanding of the epidemiology of pneumococcal infections still required their identification to determine where different serotypes spread, as well as the variable invasiveness of different serotypes. Understanding the prevalence of various serotypes was also critical to the development of pneumococcal vaccines to prevent invasive infections.

The Quellung reaction has been used to identify the 93 known capsular serotypes of Streptococcus pneumoniae in diagnostic settings, but in recent years it has been challenged by the latex agglutination method, and further by molecular typing techniques such as the polymerase chain reaction, which detect DNA and therefore target genetic differences between serotypes.[7]


  1. ^ Fisher, Bruce; Harvey, Richard P.; Champe, Pamela C. Lippincott's Illustrated Reviews: Microbiology (Lippincott's Illustrated Reviews Series). Hagerstwon, MD: Lippincott Williams & Wilkins. p. 340. ISBN 0-7817-8215-5. 
  2. ^ Neufeld, F. (1902). "Ueber die Agglutination der Pneumokokken und uber die Theorien der Agglutination". Zeitschrift für Hygiene Infektionskrankheiten. 40: 54–72. doi:10.1007/bf02140530. 
  3. ^ Sabin, Albert B. (May 20, 1933). "Immediate Pneumococcus Typing Directly from Sputum by the Neufeld Reaction". Journal of the American Medical Association. 100 (20): 1584–1586. doi:10.1001/jama.1933.02740200018004. 
  4. ^ Beckler, Edith; MacLeod, Patricia (November 1934). "The Neufeld Method of Pneumococcus Type Determination as Carried Out in a Public Health Laboratory: A Study of 760 Typings" (PDF). Journal of Clinical Investigation. 13 (6): 901–907. doi:10.1172/jci100634. PMC 436037free to read. PMID 16694257. Retrieved 9 March 2016. 
  5. ^ Griffith, Fred (January 1928). "The Significance of Pneumococcal Types" (PDF). Journal of Hygiene. 27 (2): 113–159. doi:10.1017/s0022172400031879. PMC 2167760free to read. PMID 20474956. Retrieved 10 March 2016. 
  6. ^ Avery, Oswald T.; MacLeod, Colin M.; McCarty, Maclyn (February 1, 1944). "Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types - Induction of Transformation by a Desoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III" (PDF). Journal of Experimental Medicine. 79 (2): 137–158. doi:10.1084/jem.79.2.137. PMC 2135445free to read. PMID 19871359. Retrieved 10 March 2016. 
  7. ^ PCR Deduction of Pneumococcal Serotypes Archived September 4, 2009, at the Wayback Machine.. Center for Disease Control. Retrieved October 22, 2010.

Further reading[edit]

  • Park, I. H., Pritchard, D., Cartee, R., Brandao, A., Brandileone, M. and Nahm, M. Discovery of a new capsular serotype (6C) within serogroup 6 of Streptococcus pneumoniae. Journal of Clinical Microbiology. 2007;45:1225–1233.
  • Pai, R; Gertz, R. E.; Beall, B. (2006). "Sequential multiplex PCR approach for determining capsular serotypes of Streptococcus pneumoniae isolates". Journal of Clinical Microbiology. 44: 124–131. doi:10.1128/jcm.44.1.124-131.2006. 
  • Austrian, R (1976). "The Quellung Reaction, a Neglected Microbiologic Technique". Mount Sinai Journal of Medicine. 43: 699–709.