{"id":3195,"date":"2017-02-28T04:05:56","date_gmt":"2017-02-28T09:05:56","guid":{"rendered":"http:\/\/allphasepharma.com\/dir\/?p=3195"},"modified":"2025-09-20T19:12:11","modified_gmt":"2025-09-21T01:12:11","slug":"cmv-connections-paul-bunnell-negative-mononucleosis-changelings","status":"publish","type":"post","link":"https:\/\/allphasepharma.com\/dir\/2017\/02\/28\/3195\/cmv-connections-paul-bunnell-negative-mononucleosis-changelings\/","title":{"rendered":"CMV Connections: Paul-Bunnell Negative Mononucleosis and \u2018Changelings\u2019"},"content":{"rendered":"

\"\"<\/a><\/p>\n

Mononuclesosis is an EBV infection that can be diagnosed with the heterophil antibody test developed by Paul and Bunnell. The test is based on the agglutination of sheep erythrocytes with the blood of EBV infected patients. P-B heterophil serology is negative in \u2018mononucleosis\u2019 caused by CMV.<\/p>\n

In this day and age we obviously have faster tests to detect the presence of these viruses; nevertheless, the Paul-Bunnell (P-B) test is still used in clinical practice. Please note the hyphen between the names; \u201cPaul\u201d is not the first name of Dr. Bunnell. P-B stands for Drs. John\u00a0Rodman\u00a0Paul and Walls\u00a0Willard\u00a0Bunnell.<\/p>\n

Also, let us not confuse Walls Willard with Sterling Bunnell, a famous hand surgeon who popularized atraumatic suturing and introduced a special technique for tendon repair and is considered a giant in the surgical arena[1]<\/sup><\/a>.<\/p>\n

While we are on the topic, a Forssman antigen test was also needed in the old days to exclude false positive P-B tests.

Is it spelled ‘heterophil’ or ‘heterophile’ (with an \u201ce\u201d at the end? Both spellings are commonly used.<\/span>\u00a0<\/p>\n<\/div>We are referring of course to Magnus John Karl August Forssman, a highly gifted multitalented researcher from Sweden who discovered that guinea pig kidney cells carry an antigen which can interfere with the P-B test. In addition to the eponymic heterophil antibody he also discovered the concept of neurotropism[2]<\/sup><\/a>. He was actually a giant in 2 areas.<\/p>\n

Werner Theodor Otto Forssman, his namesake but unrelated to Magnus as far as we can ascertain, was a German surgeon and urologist. His name is spelled For\u00df<\/strong>mann or Forssman in the literature. He made history for an act of personal bravery by performing the first cardiac catheterization, and doing so on himself. Using a rubber catheter which he advanced from an arm vein all the way into the right atrium, he demonstrated that the procedure can be done safely. He documented this feat by obtaining a CXR to verify the catheter position.\u00a0 Publication of this feat paved the way for what is now the field of invasive cardiology but it also got him fired twice; one of his employers, Sauerbruch, did not think much of his accomplishments. In 1956 Forssman was awarded the Nobel Prize.

Incidentally, Werner Forssman’s sons are quite famous in their own right: Berndt F., working as a urologist like his father, was involved in the development of extracorporeal shock wave lithotripsy, and Wolf F. was the first to isolate Atrial Natriuretic Peptide<\/span><\/p>\n<\/div><\/p>\n

The literature is replete with reports making a connection between CMV and coronary artery disease[3]<\/sup><\/a>. Early reports created much excitement, but the association could not be confirmed conclusively in larger and better designed follow-up trials.[4]<\/sup><\/a> Nonetheless, a CMV connection is not such an illogical or improbable consideration; after all, vasculitis is a well-known manifestation of VZV infection, another herpes virus. Other than CMV, Helicobacter, and Chlamydia have also been implicated as inflammation-causing agents in CAD.<\/p>\n

With CMV coronary angiitis being highly questionable, and CMV retinitis almost gone thanks to HAART, most clinicians are concerned with the virus only in transplant patients in whom CMV disease can present as enteritis, hepatitis, GvHD and a much feared and often fatal pneumonia.<\/p>\n

Similarly disastrous is congenital CMV disease of the newborn and fetus that can manifest in many different ways, as a multisystem disease or as neurosensory deafness. In this context Plotkin describes CMV as \u2018the changeling demon\u2019, an expression that sent us off on another journey into linguistics [5]<\/sup><\/a>.<\/p>\n

\u2018Changelings\u2019 are children that \u2013 according to mythology and old wives tales – were \u2018exchanged\u2019 at birth by fairies and trolls; they are not ordinary babies but seemingly come from another world. The German word for it is \u2018Wechselbalg\u2019 which means \u2018exchanged child\u2019. \u2018Balg\u2019 is an old Germanic word which has several meanings, all obliquely descriptive of the CMV-affected child.<\/p>\n

First, a \u2018Balg\u2019 is a derogatory term for a small child with the connotation of \u2018out of wedlock\u2019. The \u2018Balg\u2019 is also an animal skin, something that is used to cover a doll or stuffed animal. Thirdly, a \u2018Balg\u2019 means bellows, the extensible accordion-like device to blow air or oxygen into furnaces. Similarly, older cameras may have a \u2018Balg\u2019 or folding bellows that hold the retractable lens. Last but not least, the verb \u2018sich balgen\u2019 describes the fighting or rough-housing jostle between small children. This is probably the only rather non-pejorative use of the \u2018Balg\u2019 root word.<\/p>\n

Okay, you get the jist. Furtively exchanged by fairies, of unclear descent, with mental retardation and physical stigmata of disease, these abnormal kids appeared to be \u2018changelings\u2019, indeed. Something supernatural was going on with these \u2018changelings\u2019.<\/p>\n

We really have no effective treatment as yet for CMV congenital infection. The use of post-partum valganciclovir does not dramatically change the outcome; the benefit with even long-duration post-natal\u00a0therapy is moderate[6]<\/sup><\/a>. Nonetheless, testing pregnant women for CMV serostatus should become routine, followed by hygienic advice for CMV-negative mothers[7]<\/sup><\/a>. Seroconversion rates increase with age but the delayed exposure to CMV in modern society actually increases the risk of late exposure notably during the years of possible child-bearing.<\/p>\n

When prevention with hygienic measures fails, early antiviral intervention would seem the best chance for a good outcome. Let\u2019s hope that newer anti-CMV drugs, safe enough to use in pregnancy, will do away with ‘changelings’ by banning the fairies to the forests.<\/p>\n

References
\n<\/strong>[1]<\/a> Green. Giants In Orthopaedic Surgery: Sterling Bunnell MD.\u00a0 Clin Orthop Relat Res (2013) 471:3750
\n[2]<\/a> Forssman, J. (1898) Uber die Ursachen welche die Wachstumrichtung der peripheren Nervenfasern bei der Regeneration bestimmen. Beitr. Patholog. Anat. 24: 56
\n[3]<\/a> J Danesh. Chronic infection and coronary heart disease: is there a link? Lancet, <\/em>1997; 350: 430
\n[4]<\/a> Z Naing. Is cytomegalovirus infection causative for coronary heart disease? \u00a0Under the Microscope. Microbiology Australia 2013 10.1071\/MA13045: 135
\n[5]<\/a> S Plotkin. Vaccination against cytomegalovirus, the changeling demon. Pediatr Infect Dis J.\u00a01999; 18: 313
\n[6]<\/a> D Kimberlin. Valganciclovir for Symptomatic Congenital Cytomegalovirus Disease. NEJM 2015; 372: 933
\n[7]<\/a> http:\/\/www.jwatch.org\/na42777\/2016\/11\/15\/value-screening-congenital-cytomegalovirus-infection?query=topic_pedinf&jwd=000020047323&jspc=ID<\/p>\n","protected":false},"excerpt":{"rendered":"

Mononuclesosis is an EBV infection that can be diagnosed with the heterophil antibody test developed by Paul and Bunnell. The test is based on the agglutination of sheep erythrocytes with the blood of EBV infected patients. P-B heterophil serology is negative in \u2018mononucleosis\u2019 caused by CMV. In this day and Continue reading CMV Connections: Paul-Bunnell Negative Mononucleosis and \u2018Changelings\u2019<\/span>→<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":3197,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":true,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[140],"tags":[1271,1998,403,1999,1989,1991,1987,1978,31,2000,1974,1972,1990,1973,1932,1952,1984,1976,1981,1979,1996,1583,1977,1983,1997,1985,1994,1993,1982,1980,2001,1995,1986,1975,1988,1992],"class_list":["post-3195","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-interesting_facts","tag-allphase-pharma-consulting","tag-anp","tag-antibiotic-blog","tag-atrial-natriuretic-peptide","tag-balg-etymology","tag-cad","tag-changeling","tag-chlamydia","tag-cmv","tag-cmv-coronary-angiitis","tag-cmv-enteritis","tag-cmv-hepatitis","tag-cmv-in-pregnancy","tag-cmv-pneumonia","tag-cmv-prophylaxis","tag-cmv-retinitis","tag-congenital-cmv","tag-ebv","tag-forssman-antigen","tag-gvhd","tag-hand-surgery","tag-harald-reinhart","tag-helicobacter","tag-heterophil-antibody","tag-lithotrypsy","tag-neurosensory-hearing-loss","tag-neurotropism","tag-nobel-prize","tag-paul-bunnel-test","tag-sauerbruch","tag-stanley-plotkin","tag-sterling-bunnell","tag-valganciclovir","tag-vzv","tag-wechselbalg","tag-werner-forssman"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2017\/02\/CMV-connections-slider.jpg?fit=640%2C180&ssl=1","jetpack_shortlink":"https:\/\/wp.me\/p4KWFr-Px","jetpack_sharing_enabled":true,"jetpack-related-posts":[{"id":3131,"url":"https:\/\/allphasepharma.com\/dir\/2017\/02\/02\/3131\/monoclonal-pursuit-cmv-therapeutic\/","url_meta":{"origin":3195,"position":0},"title":"The Monoclonal Pursuit of the Next CMV Therapeutic","author":"Harald","date":"February 2, 2017","format":false,"excerpt":"There is no doubt that immunity to human cytomegalovirus (CMV) is both cell-and antibody-mediated. 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