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October 1965, Vol 110, No. 4 >
Article | October 1965

Studies of the Natural History and Prevention of Rubella FREE

ROBERT H. GREEN, MD; MICHAEL R. BALSAMO, MD; JOAN P. GILES, MD; SAUL KRUGMAN, MD; GEORGE S. MIRICK, MD
[+] Author Affiliations

Received for publication July 12, 1965.

Reprint requests to Department of Medicine, New York University School of Medicine, New York, NY 10016 (Dr. Green).


Am J Dis Child. 1965;110(4):348-365. doi:10.1001/archpedi.1965.02090030368003.
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Comments

ALTHOUGH RUBELLA is almost invariably a mild, self-limited disease seldom followed by complications or sequelae of any kind, numerous studies have established that at least 15% to 20% of the offspring of women who contract German measles during the first trimester of pregnancy are afflicted with one or more serious and grossly discernible congenital malformations.1-8 Moreover, if audiometric studies are done, an additional 20% to 30% of such children are found to have some impairment of hearing.9 The earlier in pregnancy that maternal rubella occurs, the greater is the hazard to the fetus; thus, 50% or more of the children born of women contracting rubella during the first four weeks of pregnancy may have gross congenital

REFERENCES

1 +
Gregg, N.McA.:  Congenital Cataract Following German Measles in the Mother , Trans Ophth Soc Aust 3:35-46, 1941;.
2 +
Gregg, N.McA., et al:  Occurrence of Congenital Defects in Children Following Maternal Rubella During Pregnancy , Med J Aust 2:122-126, 1945;.
3 +
Greenberg, M.; Pellitteri, O.; and Barton, J.:  Frequency of Defects in Infants Whose Mothers Had Rubella During Pregnancy , JAMA 165:675-678, 1957;.
4 +
Ingalls, T.H.:  German Measles and German Measles in Pregnancy , J Dis Child 93:555-558, 1957;.
5 +
Manson, M.M.; Logan, W.P.D.; and Loy, R.M.: Rubella and Other Virus Infections During Pregnancy. Reports on Public Health and Medical Subjects No. 101, Ministry of Health, Her Majesty's Stationery Office, 1960.
6 +
Michaels, R.H., and Mellin, G.W.:  Prospective Experience With Maternal Rubella and the Associated Congenital Malformations , Pediatrics 26:200-209, 1960;.
7 +
Lock, F.R., et al:  Incidence of Anomalous Development Following Maternal Rubella , Amer J Obstet Gynec 81:451-464, 1961;.
8 +
Lindstrom, R.:  Rubella During Pregnancy: A Follow-Up Study of Children After an Epidemic of Rubella in Sweden, 1951, With Additional Investigations on Prophylaxis and Treatment of Maternal Rubella , Acta Paediat 51 ( (supp 133) ):1-110, 1962;.
9 +
Jackson, A.D.M., and Fisch, L.:  Deafness Following Maternal Rubella: Results of a Prospective Investigation , Lancet 2:1,241-1,247, 1958;.
10 +
Hill, A.B., et al:  Virus Diseases in Pregnancy and Congenital Defects , Brit J Prev Soc Med 12: 1-7, 1958;.
11 +
Ingalls, T.H., et al:  Rubella: Its Epidemiology and Teratology , Amer J Med Sci 239:363-383, 1960;.
12 +
Brody, J.A., et al:  Rubella Epidemic on St. Paul Island in the Pribilofs, 1963: I. Epidemiologic, Clinical, and Serologic Findings , JAMA 191:619-623, 1965;.
13 +
Babbott, F.L., Jr.; Rodenberger, B.M.; and Ingalls, T.H.:  Rubella: Morbidity in a Schoolboy Population, 1935-1959, and a Comparison With Measles, Mumps, and Chickenpox , JAMA 178: 542-546, 1961;.
14 +
Buescher, E.L., et al:  Association of R.A. Agent With Rubella, Scarlet Fever, and Other Disease in Recruits , abstracted, Fed Proc 21:466, 1962;.
15 +
Parkman, P.D.; Buescher, E.L.; and Artenstein, M.S.:  Recovery of Rubella Virus From Army Recruits , Proc Soc Exp Biol Med 111: 225-230, 1962;.
16 +
Heggie, A.D., and Robbins, F.C.:  Rubella in Naval Recruits: A Virologic Study , New Eng J Med 271:231-234, 1964;.
17 +
Peczenik, A., and Gauld, J.R.:  Rubella at a Military Installation , Arch Environ Health 6:657-663, 1963;.
18 +
Miller, L.F.: Personal communication to the author.
19 +
Pampiglione, G.; Young, S.E.J.; and Ramsay, A.M.:  Neurological and Electroencephalographic Problems of the Rubella Epidemic of 1962 , Brit Med J 2:1300-1302, 1963;.
20 +
Sherman, F.E.; Michaels, R.H.; and Kenny, F.M.:  Acute Encephalopathy (Encephalitis) Complicating Rubella: Report of Cases With Virologic Studies, Cortisol-Production Determinations, and Observations at Autopsy , JAMA 192:675-681, 1965;.
21 +
Wallace, S.J.:  Thrombocytopenic Purpura After Rubella , Lancet 1:139-141, 1963;.
22 +
Johnson, R.E., and Hall, A.P.:  Rubella Arthritis: Report of Cases Studied by Latex Tests , New Eng J Med 258:743-745, 1958;.
23 +
Kantor, T.G., and Tanner, M.:  Rubella Arthritis and Rheumatoid Arthritis , Arthritis Rheum 5:378-383, 1962;.
24 +
Sever, J.L.; Schiff, G.M.; and Traub, R.G.:  Rubella Virus , JAMA 182:663-671, 1962;.
25 +
Veronelli, J.A.; Maassab, H.F.; and Hennessy, A.V.:  Isolation in Tissue Culture of an Interfering Agent From Patients With Rubella , Proc Soc Exp Biol Med 111:472-476, 1962;.
26 +
Sigurdardottir, B., et al:  Association of Virus With Cases of Rubella Studied in Toronto: Propagation of the Agent and Transmission to Monkeys , Canad Med Ass J 88:128-132, 1963;.
27 +
Balsamo, M.R., et al:  Laboratory and Clinical Studies of Rubella , abstracted, Fed Proc 22: 208, 1963;.
28 +
Weller, T.H., and Neva, F.A.:  Propagation in Tissue Culture of Cytopathic Agents From Patients With Rubella-Like Illness , Proc Soc Exp Biol 111:215-225, 1962;.
29 +
Poltkin, S.A.; Dudgeon, J.A.; and Ramsay, A.M.:  Laboratory Studies on Rubella and the Rubella Syndrome , Brit Med J 2:1296-1299, 1963;.
30 +
McCarthy, K.; Taylor-Robinson, C.H.; and Pillinger, S.E.:  Isolation of Rubella Virus From Cases in Britain , Lancet 2:593-598, 1963;.
31 +
Selzer, G.:  Virus Isolation, Inclusion Bodies, and Chromosomes in Rubella-Infected Human Embryo , Lancet 2:336-337, 1963;.
32 +
Weller, T.H.; Alford, C.A., Jr.; and Neva, F.A.:  Retrospective Diagnosis by Serologic Means of Congenitally Acquired Rubella Infections , New Eng J Med 270:139-1041, 1964;.
33 +
Green, R.H., et al:  Studies on the Experimental Transmission, Clinical Course, Epidemiology and Prevention of Rubella , Trans Ass Amer Physicians 77:118-125, 1964;.
34 +
Kay, H.E.M., et al:  Congenital Rubella Infection of a Human Embryo , Brit Med J 2:166-167, 1964;.
35 +
Neva, F.A., and Weller, T.H.:  Rubella Interferon and Factors Influencing the Indirect Neutralization Test for Rubella Antibody , J Immun 93:466-473, 1964;.
36 +
Alford, C.A., Jr.; Neva, F.A.; and Weller, T.H.:  Virologic and Serologic Studies on Human Products of Conception After Maternal Rubella , New Eng J Med 271:1275-1281, 1964;.
37 +
Taylor-Robinson, C.H., et al:  Plaque Formation by Rubella Virus , Lancet 1:1364-1365, 1964;.
38 +
Dudgeon, J.A.; Butler, N.R.; and Plotkin, S.A.:  Further Serological Studies on the Rubella Syndrome , Brit Med J 2:155-160, 1964;.
39 +
Parkman, P.D., et al:  Studies of Rubella: I. Properties of the Virus , J Immun 93:595-607, 1964;.
40 +
Parkman, P.D., et al:  Studies of Rubella: II. Neutralization of the Virus , J Immun 93:608-617, 1964;.
41 +
Brown, G.C., et al:  Rubella Antibodies in Human Serum: Detection by the Indirect Fluorescent-Antibody Technique , Science 145:943-944, 1964;.
42 +
Sever, J.L.; Schiff, G.M.; and Huebner, R.J.:  Frequency of Rubella Antibody Among Pregnant Women and Other Human and Animal Populations , Obstet Gynec 23:153-159, 1964;.
43 +
Sever, J.L., et al:  Rubella Complement Fixation Tests , Science 148:385-387, 1965;.
44 +
Phillips, C.A., et al:  Isolation of Rubella Virus: An Epidemic Characterized by Rash and Arthritis , JAMA 191:615-618, 1965;.
45 +
Rudolph, A.J., et al:  Transplacental Rubella Infection in Newly Born Infants , JAMA 191:843-845, 1965;.
46 +
Horstmann, D.M.:  Rubella and the Rubella Syndrome: New Epidemiologic and Virologic Observations , Calif Med 102:397-403, 1965;.
47 +
Ward, R., et al:  Infectious Hepatitis: Studies on Its Natural History and Prevention , New Eng J Med 258:407-416, 1958;.
48 +
Buescher, E.L., and Parkman, P.D.: Personal communication to the author.
49 +
Hiro, Y., and Tasaka, S.:  Die roteln sind eine viruskrankheit , Mschr Kinderheilk 76:328-332, 1938;.
50 +
Anderson, S.G.:  Experimental Rubella in Human Volunteers , J Immun 62:29-40, 1949;.
51 +
Krugman, E., et al:  Studies on Rubella Immunization: I. Demonstration of Rubella Without Rash , JAMA 151:285-288, 1953;.
52 +
Fuerst, Harold, T.: Personal communication to the author.
53 +
Krugman, S., and Ward, R.:  Rubella: Demonstration of Neutralizing Antibody in Gamma Globulin and Re-evaluation of Rubella Problem , New Eng J Med 259:16-19, 1958;.
54 +
Grayston, J.T., and Watten, R.H.:  Epidemic Rubella in Taiwan, 1957-1958: III. Gamma Globulin in the Prevention of Rubella , New Eng J Med 261:1145-1150, 1959;.
55 +
Lundstrom, R.; Thoren, C.; and Blomquist, B.:  Gamma Globulin Against Rubella in Pregnancy: I. Prevention of Maternal Rubella by Gamma Globulin and Convalescent Gamma Globulin: A Follow-Up Study , Acta Paediat 50:444-452, 1961;.
56 +
Anderson, S.G., and McLorinan, H.:  Convalescent Rubella Gamma Globulin as a Possible Prophylactic Against Rubella , Med J Aust 1:182-185, 1953;.
57 +
Korns, R.F.:  Prophylaxis of German Measles With Immune Serum Globulin , J Infect Dis 90:183-189, 1952;.
58 +
Houser, H.B., and Schalet, N.:  Prevention of Rubella With Gamma Globulin , Clin Res 6: 281-282, 1958;.
59 +
Landon, J.F., et al:  Efficacy of Gamma Globulin in Prevention of German Measles , New York J Med 5:21-23, 1949;.
60 +
Brody, J.A.; Sever, J.L.; and Schiff, G.M.:  Prevention of Rubella by Gamma Globulin During an Epidemic in Barrow, Alaska, in 1964 , New Eng J Med 272:127-129, 1965;.
61 +
Schiff, G.M.; Sever, J.L.; and Huebner, R.J.:  Rubella Virus: Neutralizing Antibody in Commercial Gamma Globulin , Science 142:58-60, 1963;.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

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References

1 +
Gregg, N.McA.:  Congenital Cataract Following German Measles in the Mother , Trans Ophth Soc Aust 3:35-46, 1941;.
2 +
Gregg, N.McA., et al:  Occurrence of Congenital Defects in Children Following Maternal Rubella During Pregnancy , Med J Aust 2:122-126, 1945;.
3 +
Greenberg, M.; Pellitteri, O.; and Barton, J.:  Frequency of Defects in Infants Whose Mothers Had Rubella During Pregnancy , JAMA 165:675-678, 1957;.
4 +
Ingalls, T.H.:  German Measles and German Measles in Pregnancy , J Dis Child 93:555-558, 1957;.
5 +
Manson, M.M.; Logan, W.P.D.; and Loy, R.M.: Rubella and Other Virus Infections During Pregnancy. Reports on Public Health and Medical Subjects No. 101, Ministry of Health, Her Majesty's Stationery Office, 1960.
6 +
Michaels, R.H., and Mellin, G.W.:  Prospective Experience With Maternal Rubella and the Associated Congenital Malformations , Pediatrics 26:200-209, 1960;.
7 +
Lock, F.R., et al:  Incidence of Anomalous Development Following Maternal Rubella , Amer J Obstet Gynec 81:451-464, 1961;.
8 +
Lindstrom, R.:  Rubella During Pregnancy: A Follow-Up Study of Children After an Epidemic of Rubella in Sweden, 1951, With Additional Investigations on Prophylaxis and Treatment of Maternal Rubella , Acta Paediat 51 ( (supp 133) ):1-110, 1962;.
9 +
Jackson, A.D.M., and Fisch, L.:  Deafness Following Maternal Rubella: Results of a Prospective Investigation , Lancet 2:1,241-1,247, 1958;.
10 +
Hill, A.B., et al:  Virus Diseases in Pregnancy and Congenital Defects , Brit J Prev Soc Med 12: 1-7, 1958;.
11 +
Ingalls, T.H., et al:  Rubella: Its Epidemiology and Teratology , Amer J Med Sci 239:363-383, 1960;.
12 +
Brody, J.A., et al:  Rubella Epidemic on St. Paul Island in the Pribilofs, 1963: I. Epidemiologic, Clinical, and Serologic Findings , JAMA 191:619-623, 1965;.
13 +
Babbott, F.L., Jr.; Rodenberger, B.M.; and Ingalls, T.H.:  Rubella: Morbidity in a Schoolboy Population, 1935-1959, and a Comparison With Measles, Mumps, and Chickenpox , JAMA 178: 542-546, 1961;.
14 +
Buescher, E.L., et al:  Association of R.A. Agent With Rubella, Scarlet Fever, and Other Disease in Recruits , abstracted, Fed Proc 21:466, 1962;.
15 +
Parkman, P.D.; Buescher, E.L.; and Artenstein, M.S.:  Recovery of Rubella Virus From Army Recruits , Proc Soc Exp Biol Med 111: 225-230, 1962;.
16 +
Heggie, A.D., and Robbins, F.C.:  Rubella in Naval Recruits: A Virologic Study , New Eng J Med 271:231-234, 1964;.
17 +
Peczenik, A., and Gauld, J.R.:  Rubella at a Military Installation , Arch Environ Health 6:657-663, 1963;.
18 +
Miller, L.F.: Personal communication to the author.
19 +
Pampiglione, G.; Young, S.E.J.; and Ramsay, A.M.:  Neurological and Electroencephalographic Problems of the Rubella Epidemic of 1962 , Brit Med J 2:1300-1302, 1963;.
20 +
Sherman, F.E.; Michaels, R.H.; and Kenny, F.M.:  Acute Encephalopathy (Encephalitis) Complicating Rubella: Report of Cases With Virologic Studies, Cortisol-Production Determinations, and Observations at Autopsy , JAMA 192:675-681, 1965;.
21 +
Wallace, S.J.:  Thrombocytopenic Purpura After Rubella , Lancet 1:139-141, 1963;.
22 +
Johnson, R.E., and Hall, A.P.:  Rubella Arthritis: Report of Cases Studied by Latex Tests , New Eng J Med 258:743-745, 1958;.
23 +
Kantor, T.G., and Tanner, M.:  Rubella Arthritis and Rheumatoid Arthritis , Arthritis Rheum 5:378-383, 1962;.
24 +
Sever, J.L.; Schiff, G.M.; and Traub, R.G.:  Rubella Virus , JAMA 182:663-671, 1962;.
25 +
Veronelli, J.A.; Maassab, H.F.; and Hennessy, A.V.:  Isolation in Tissue Culture of an Interfering Agent From Patients With Rubella , Proc Soc Exp Biol Med 111:472-476, 1962;.
26 +
Sigurdardottir, B., et al:  Association of Virus With Cases of Rubella Studied in Toronto: Propagation of the Agent and Transmission to Monkeys , Canad Med Ass J 88:128-132, 1963;.
27 +
Balsamo, M.R., et al:  Laboratory and Clinical Studies of Rubella , abstracted, Fed Proc 22: 208, 1963;.
28 +
Weller, T.H., and Neva, F.A.:  Propagation in Tissue Culture of Cytopathic Agents From Patients With Rubella-Like Illness , Proc Soc Exp Biol 111:215-225, 1962;.
29 +
Poltkin, S.A.; Dudgeon, J.A.; and Ramsay, A.M.:  Laboratory Studies on Rubella and the Rubella Syndrome , Brit Med J 2:1296-1299, 1963;.
30 +
McCarthy, K.; Taylor-Robinson, C.H.; and Pillinger, S.E.:  Isolation of Rubella Virus From Cases in Britain , Lancet 2:593-598, 1963;.
31 +
Selzer, G.:  Virus Isolation, Inclusion Bodies, and Chromosomes in Rubella-Infected Human Embryo , Lancet 2:336-337, 1963;.
32 +
Weller, T.H.; Alford, C.A., Jr.; and Neva, F.A.:  Retrospective Diagnosis by Serologic Means of Congenitally Acquired Rubella Infections , New Eng J Med 270:139-1041, 1964;.
33 +
Green, R.H., et al:  Studies on the Experimental Transmission, Clinical Course, Epidemiology and Prevention of Rubella , Trans Ass Amer Physicians 77:118-125, 1964;.
34 +
Kay, H.E.M., et al:  Congenital Rubella Infection of a Human Embryo , Brit Med J 2:166-167, 1964;.
35 +
Neva, F.A., and Weller, T.H.:  Rubella Interferon and Factors Influencing the Indirect Neutralization Test for Rubella Antibody , J Immun 93:466-473, 1964;.
36 +
Alford, C.A., Jr.; Neva, F.A.; and Weller, T.H.:  Virologic and Serologic Studies on Human Products of Conception After Maternal Rubella , New Eng J Med 271:1275-1281, 1964;.
37 +
Taylor-Robinson, C.H., et al:  Plaque Formation by Rubella Virus , Lancet 1:1364-1365, 1964;.
38 +
Dudgeon, J.A.; Butler, N.R.; and Plotkin, S.A.:  Further Serological Studies on the Rubella Syndrome , Brit Med J 2:155-160, 1964;.
39 +
Parkman, P.D., et al:  Studies of Rubella: I. Properties of the Virus , J Immun 93:595-607, 1964;.
40 +
Parkman, P.D., et al:  Studies of Rubella: II. Neutralization of the Virus , J Immun 93:608-617, 1964;.
41 +
Brown, G.C., et al:  Rubella Antibodies in Human Serum: Detection by the Indirect Fluorescent-Antibody Technique , Science 145:943-944, 1964;.
42 +
Sever, J.L.; Schiff, G.M.; and Huebner, R.J.:  Frequency of Rubella Antibody Among Pregnant Women and Other Human and Animal Populations , Obstet Gynec 23:153-159, 1964;.
43 +
Sever, J.L., et al:  Rubella Complement Fixation Tests , Science 148:385-387, 1965;.
44 +
Phillips, C.A., et al:  Isolation of Rubella Virus: An Epidemic Characterized by Rash and Arthritis , JAMA 191:615-618, 1965;.
45 +
Rudolph, A.J., et al:  Transplacental Rubella Infection in Newly Born Infants , JAMA 191:843-845, 1965;.
46 +
Horstmann, D.M.:  Rubella and the Rubella Syndrome: New Epidemiologic and Virologic Observations , Calif Med 102:397-403, 1965;.
47 +
Ward, R., et al:  Infectious Hepatitis: Studies on Its Natural History and Prevention , New Eng J Med 258:407-416, 1958;.
48 +
Buescher, E.L., and Parkman, P.D.: Personal communication to the author.
49 +
Hiro, Y., and Tasaka, S.:  Die roteln sind eine viruskrankheit , Mschr Kinderheilk 76:328-332, 1938;.
50 +
Anderson, S.G.:  Experimental Rubella in Human Volunteers , J Immun 62:29-40, 1949;.
51 +
Krugman, E., et al:  Studies on Rubella Immunization: I. Demonstration of Rubella Without Rash , JAMA 151:285-288, 1953;.
52 +
Fuerst, Harold, T.: Personal communication to the author.
53 +
Krugman, S., and Ward, R.:  Rubella: Demonstration of Neutralizing Antibody in Gamma Globulin and Re-evaluation of Rubella Problem , New Eng J Med 259:16-19, 1958;.
54 +
Grayston, J.T., and Watten, R.H.:  Epidemic Rubella in Taiwan, 1957-1958: III. Gamma Globulin in the Prevention of Rubella , New Eng J Med 261:1145-1150, 1959;.
55 +
Lundstrom, R.; Thoren, C.; and Blomquist, B.:  Gamma Globulin Against Rubella in Pregnancy: I. Prevention of Maternal Rubella by Gamma Globulin and Convalescent Gamma Globulin: A Follow-Up Study , Acta Paediat 50:444-452, 1961;.
56 +
Anderson, S.G., and McLorinan, H.:  Convalescent Rubella Gamma Globulin as a Possible Prophylactic Against Rubella , Med J Aust 1:182-185, 1953;.
57 +
Korns, R.F.:  Prophylaxis of German Measles With Immune Serum Globulin , J Infect Dis 90:183-189, 1952;.
58 +
Houser, H.B., and Schalet, N.:  Prevention of Rubella With Gamma Globulin , Clin Res 6: 281-282, 1958;.
59 +
Landon, J.F., et al:  Efficacy of Gamma Globulin in Prevention of German Measles , New York J Med 5:21-23, 1949;.
60 +
Brody, J.A.; Sever, J.L.; and Schiff, G.M.:  Prevention of Rubella by Gamma Globulin During an Epidemic in Barrow, Alaska, in 1964 , New Eng J Med 272:127-129, 1965;.
61 +
Schiff, G.M.; Sever, J.L.; and Huebner, R.J.:  Rubella Virus: Neutralizing Antibody in Commercial Gamma Globulin , Science 142:58-60, 1963;.

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