key: cord-0252224-vzy76cyk authors: Hedley-Whyte, John; Milamed, Debra R. title: Measles: Progress and Failure date: 2021-07-08 journal: Ulster Med J DOI: nan sha: ca9b547756d96d366e4d0b25142c13e0afcbcf1d doc_id: 252224 cord_uid: vzy76cyk nan "Every boy should know about Herd Immunity", replied Professor Rutherford Morison to me 1 at the Annual (1938) Dipping of Cheviot sheep. My question to Professor Rutherford Morison had been suggested by my maternal grandfather who was a farmer and landowner of fields near Newcastle-upon-Tyne, where my father had been an Assistant Surgeon to Professor Rutherford Morison. As surgeons they both knew that I should be away from our home where my mother was being treated for post-partum thrombosis. Aged almost 5, I was staying with another famous surgeon, George A. Mason, later CBE, and his family nearby on Cheviot's north side. My first meeting with Director Ted Badger was in Hut 1, Musgrave Park 1,2,3,4 . He asked me if I had had measles. I replied, "Yes, I had been treated in the dark to protect my conjunctivae". "Good," Badger replied. That was what ophthalmologist Rycroft-my brother's godfather-had told him 5, 6 . I asked Badger if he had missed the Faroes in his small yacht sail from Yale 7 . "Yes," he said. "We are going to use measles in our counter-attack against your father's accusers, who are trying to have him court-martialed for attempting to obtain foods rich in vitamin A" 5, 8 . I, said Badger, am only a stand-in for Charles A. Janeway (CAJ) (Fig. 1) , who was told to stay in Boston at Harvard to continue research with John F. Enders 9,10 on the immunological control of mumps and measles in addition to his own work on plasma fractionation of blood 11, 12, 13 . This had been ordered by CAJ's neighbor, U.S. Secretary of War Henry L. Stimson (Fig 2) . Badger informed me that "The Stimsons own thousands of acres next to the Janeways' estate in the Adirondacks. The Stimsons also have a Long Island estate with its own polo field and Highland games" 14 (Fig.1) (Fig.2) . (Table 1) . Gamma globulin (human immune serum globulin) obtained as a product of human plasma fractionation was an effective means of prevention or amelioration of measles 11, 12, 13 . Measles never became a serious military problem during World War II 29, 30, 31, 32, 38 (Table 1) . United Kingdom, the United States and a number of other countries being declared measles-free 51, 52 . The World Health Organization (WHO) defines elimination of measles as "the interruption of measles transmission in a defined geographical area that has lasted at least 12 months" 53 . Because of its high infectivity, "the herd protection threshold for measles is the highest of all vaccine-preventable diseases and varies in different settings ranging from 89% to 94%" 53 . Now in 2020, Boston has registered two confirmed cases of measles in the past 4 months 54 (Fig. 3) . Air travel to both the U.K. and U.S. warrants closer monitoring: Koplick spots are easily recognizable. The WHO has reported global annual incidence of measles of approximately 6,733,000 cases resulting in 109,638 deaths as recently as 2017 53, 62, 63 . Complications such as blindness, encephalitis, pneumonia, as well as death, are more frequent among malnourished or vitamin-A deficient children, or those with immune systems weakened by HIV/AIDS or other causes 51, 52, 62, 63 . Measles may disrupt the function of F protein and result in neurological sequelae including "primary measles encephalitis, acute post measles encephalitis, subacute sclerosing panencephalitis (SSPE) and measles inclusion body encephalitis (MIBE)" 64 . where clinical vitamin A deficiency remains an ongoing public health concern 5 . While WHO has reported an 88 percent global decrease in incidence of measles during the period 2000-2016, from 145 to 18 cases per million persons, by 2019 the incidence had risen again to 120 cases per million, its highest rate since 2001 65 . Sixty-two percent of countries reporting in 2019 included viral genotype information. The WHO reported that twenty out of twenty-four recognized measles genotypes could be eliminated by vaccination 65 . Global estimates of measles mortality increased nearly 50 percent between 2016, which had the lowest rates recorded since 2000, and 2019. Failure to vaccinate is recognized as the main cause of resurgence 65 . The 2020 coronavirus pandemic has led to further decreases in vaccination and surveillance 66 . The late Distinguished Professor Emerita of Neuropathology Dame Ingrid Allen (Fig. 4) and her colleagues, including Professor Bertus K. Rima of the Center for Experimental Medicine, Queen's University Belfast, identified the primary cell types infected with measles virus as those of the immune system-lymphocytes, macrophages and dendritic cells. In addition, they identified a small number of infected epithelial cells 67 . This group also studied the role of the F-gene as a major determinant of neurovirulence 67 . Professor Allen established the Regional Neuropathology Service for Northern Ireland in 1972 and served as its first leader. In 2006 she began a review of Pathology Services in Northern Ireland which led to the establishment of the Northern Ireland Pathology Network 68 . Post-measles immunosuppression and its long-term immunologic sequelae were elucidated. Measles vaccination (MMR), using Enders' attenuated Edmonston strain aids prevention of all infectious disease and promotes "polymicrobial herd immunity" 69, 70 . Recent work by Michael J. Mina, now at Harvard University, and his U.S. and international colleagues, demonstrates that measles causes "elimination of 11 to 73% of the antibody repertoire across individuals" 69, 70 . The impairment of immune cells increases the risk of secondary infection 61 . In Northern Ireland, the steepest decline in reported cases occurred after the introduction in 1988 of the combined measles-mumps-rubella (MMR) vaccine given at age 15 months 61 . This was followed by a UK-wide campaign for vaccination of all school children in 1994 61 . More recently in Northern Ireland, as in the U.S., cases are mostly "imported" by air-travel 60,61 . Professor Dame Ingrid Allen (1932-2020), oil on canvas, 108 cm x 93.5 cm, No. QUB 6, by Tom Hallifax (1965-). From the collection of the Naughton Gallery, Queen's University, Belfast and reproduced with permission. UMJ is an open access publication of the Ulster Medical Society (http://www.ums.ac.uk). The Ulster Medical Society grants to all users on the basis of a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International Licence the right to alter or build upon the work non-commercially, as long as the author is credited and the new creation is licensed under identical terms. leading to many of the deaths attributable to measles 69, 70 . Adaptive immunity will also play a role in determining response to coronavirus disease vaccines 71 . My Clare College Physiology tutor, E.N. Willmer, FRS, has described in detail Enders' tissue culture technique 46, 72 . Willmer opined that herd immunity for measles would require the immunity of at least 96 percent of the population. This prediction to me in 1954 occurred in the Fellows' Garden, that Willmer designed and supervised. The Cam flows past. Epidemic jaundice: Harvard's 5 th General Hospital at Musgrave Park in World War II Base Hospital No. 5 Fifth General Hospital Tuberculous scrofula: Belfast experience Aspects of vitamin A Asbestos and shipbuilding: Fatal consequences Observations made during the Epidemic of Measles on the Faroe Islands in the Year 1846 Vitamin A Requirement of Human Adults: an experimental study of vitamin A deprivation in man. A report of the Vitamin A Sub-Committee of the Accessory Food Factors Committee Measles virus. Historical review. Isolation and behavior in various systems International contributions toward the conquest of polio Janeway: pediatrician to the World's Children. Boston: Children's Hospital Chemical, clinical and immunological studies on the products of human plasma fractionation. XII. The use of concentrated normal human serum gamma globulin (human immune serum globulin) on the prevention and attenuation of measles The Gamma Globulins A study in statecraft On Active Service in Peace and War New York: Privately printed The President's case. Red Cross Notes Clinical observations on the pathogenesis of tuberculosis: From a 15 year follow-up of 745 nurses Tuberculosis in nurses: clinical observations on its pathogenesis as seen in a 15 year follow-up of 745 nurses Night vision in the Army Ophthalmology in the B BIPP Treatment of War Wounds. London: Henry Frowde, Hodder and Stoughton Studies on the plasma proteins. V. The effect of concentrated solutions of human and bovine serum albumin on blood volume after acute blood loss in man Blood and blood derivatives-a new public health field Use of concentrated Human Serum gamma-globulin in the prevention and attenuation of measles Measles epidemics of variable lethality in the early 20 th century Ellis FP. The Royal Naval Medical Services. Mayne HG. The Army Medical Services. Welch S.C.R. The Royal Air Force Medical Services. London: Her Majesty's Stationery Office Official History of the Canadian Medical Services 1939-1945 Communicable Diseases Transmitted chiefly Through Respiratory and Alimentary Tracts Office of the Surgeon General Office of the Surgeon General. Medical Department, US Army; 1975. Table 29b UMJ is an open access publication of the Ulster Medical Society The Ulster Medical Society grants to all users on the basis of a Creative Commons Attribution-NonCommercial Blood Transfusion. London: Henry Frowde and Hodder & Stoughton; 1922 Transfusion of blood in malignant measles Lobar pneumonia treated by Musgrave Park physicians Our blood your money Medical Department. United States Army Office of the Surgeon General On being a pathologist: how does one plan a career, or does one? As I remember him: the biography of R.S An immunological consideration of the virus problem On the nature of virus agents Variation in the susceptibility of guinea pigs to reversed passive anaphylaxis Immunity. Principles and application in medicine and public health Applied immunology in some virus diseases. Measles (Morbili) Chemical, clinical and immunological studies on the products of human plasma fractionation. X. The concentrations of certain antibodies in globulin fractions derived from human blood plasma Propagation in tissue cultures of cytopathogenic agents from patients with measles Vaccination against measles Evaluation of measles virus Attenuated measles vaccine in children with acute leukemia Use of Edmonston attenuated measles strain. A summary of three years' experience Framework for verifying elimination of measles and rubella World Health Organization. Global Measles and Rubella Strategic Plan pdf;jsessionid=9D1A10C37 C67C3A7E652BAEC65F1D6D6?sequence=1 Measles vaccines: WHO position paper Northeastern student diagnosed with measles Public Health Agency, Northern Ireland. Data provided to the authors upon request (see acknowledgements) Historical Summary Tables covering the Period 1939-1988. Table 1. Notifiable diseases -Summary of reported cases Reported cases of notifiable diseases -United States MMWR: Summary of Notifiable Infectious Diseases Centers for Disease Control. Nationally Notifiable Infectious Diseases and Conditions. United States: Annual Tables Summary recommendations of the Advisory Committee on Immunization Practices (ACIP) Spotlight on Measles 2010: Ongoing measles outbreak in Northern Ireland following an imported case World Health Organization. News. New measles surveillance data for 2019 Neurological complications of measles (rubeola) Progress toward Regional Measles Elimination-Worldwide Report from the director of IVB: building back better for immunization in a COVID-19 world Macrophages and dendritic cells are the predominant cells infected in measles in humans. mSphere UK: The Faraday Institute for Science and Religion Longterm measles-induced immunomodulation increases overall childhood infectious disease mortality Measles virus infection diminishes preexisting antibodies that offer protection from other pathogens Immune life history, vaccination, and the dynamics of SARS-CoV-2 over the next five years Cell, tissue and organ cultures in virus research The authors wish to thank Ms. Joy Murphy, Health Protection Surveillance Officer, Information Section, BBV/STI/VPD/ I&V, Public Health Agency, Northern Ireland, for providing historical data on the incidence of measles in Northern Ireland. We wish to thank Mr. Ben Crothers, Curator and Collections Manager, the Naughton Gallery, Queen's University, Belfast, for reproduction of the portrait of the late Professor Dame Ingrid V. Allen. The authors wish to thank Mr. Philip Augusta for permission to reproduce the portrait of Professor Charles A. Janeway painted by his late father. The authors wish to thank Ms. Alina J. Morris, MLIS, Archives Program Manager, and Ms. Cindy L.Y. Chow, Executive Assistant to Dr. Gary R. Fleisher, Department of Medicine, Boston Children's Hospital, for assistance. The authors also wish to thank Professor Tweed Roosevelt, University Professor, Long Island University, for his insightful suggestions and historical perspective.