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An outbreak of measles among young adults
Liver enzymes
Fmn the Israel Defence Forces Medical Corps (L.L., T.S., G.A.), the Depzrtmentof Pediatrics, Beilimson Medical Center, Petah Tiqva (G.A.) and the Departmmt of Cmmunify Health, Cannel Hospifal, Waifi, Israel (L.M.E.). rtment of Internal Medicine B BeiPrese& alyiriations: L. L.: rtment @Infernal linson Medical Cenlei-, i%t~h Tiqva, brae!; T.S.: Medicine, Rivfra Ziv Hospital, @at, Israel; O.K.: htilufe of PedkPric Endocrinology, Beilinson Medical Center, Petah Tiqva, Israel dress reprint requests to: L. Leikwici, M.D., Department oJMedicine B, Beilinson Medical Center, Petah Tiqva 49100, Israel. Manuscript accepted January 17, 1987.
Q society for Adolescent Medicine, 1988 Published by Elsevier Science Publishing Co., Inc., 52 Vanderbilt Ave., New York, NY 10017
LElBovIQ ET AL.
a standard form. Patients without complications were hospitalized until defervescence and fading of the rash on face and upper trunk. All patients were examined again 3 days after discharge and on additional occasions if clinically indicated. Chest roentgenographs were obtained in 195 patients who had abnormal findings on physical examinationof the lungs, and x-rays of the frontal and maxillary sinuses were taken in 112 patients with headache and/or purulent nasal discharge. Sinusitis was diagnosed if there was diffuse opacification or if an air-fluid level observed in a paranasal sinus. An electrocardiogram (RCG) was obtained in 172 randomly chosen patients on the first or second day after the appearance of the rash and again 4 to 5 days later. Patients who complained of an earache with some irritation of the tympanic membrane and auditory as having otitis externa, canal were diagnos whereas those with iteration of the light reflex and a red, bulging membrane were diagnosed as having otitis media. All patients with conjunctival injection were examined by slit lamp and fluorescein staining for evidence of keratitis. A total and differential cell count, erythrocyte sedimentation rate (ESR), and microscopic examination of urine sediment were performed in all patients on the first or second day after the appearance of the rash. Serum ghttamic oxaloacetic transaminase (SGOT), lactic creatine kinase (CK), total a alkaline phosphatase were obtained on the same day in 114 randomly chosen patients. The CK isoenzymes were quantified by immunoinhibition. We measured aldolase levels in the 13 patients with the highest serum CK, and an electromyography (EMG) was performed on six patients with a high CK and aldolase. Data about immunization were ascertained from childhood immunization cards. The data were stored and analyzed using the Statistical Analysis System (14,15). Statistical significance was tested by the x2 analysis for contingency tables, a two-tailed t-test for continuous variables with a normal distribution, and by a Wilcoxonnonparametric test for other continuous variables. The hypothesis that the values of a continuous variable were randomly Chosen from a normal distribution was tested by the Kohnogorov-Smirnov statistic or by the Shapiro-Wile statistic, as appropriate (15, p. 580). Thee e values are given as multiplications Of the normal range (i.e., 1 = within normal range;
JOURNAL OF ADOLESCENT HEALTH C
Vol. 9, No. 3
Table1. ClinicalFeatures of Measles Prodrome in Young Adults Clinical feature
Cough and coryza Fever (>37.5T) Conjuctivitis Photophobia Vomiting Abdominal pains Diarrhea
Pecentage of patients loo.0 97.8 47.7 26.9 7.8 4.6 4.6
Results
(range 17-26 yr). They
per high power field) in 2.5%. Although only two patients were jaundiced, 50.9% of the pati had elevated SGOT LDH, 29.8%; and a 4). The CK was eleva elevated fraction was mined. Traces of myog of 14% of patients with patients with the highest s, 12 had an elevated serum aldolase, but no a served in the six EMGs performed.
ASLES
Percent 1234567
Enanthem Cough and coryza Koplik’s spots Conjuctivitis I-Iemorrhagic conjunctivitis Cervical lym~~~enopat~y AxiIlary lymphadenopathy Inguinal lympha~eno~at~y
99.6 99.3 98.0 47.3 2.4 47.3 6.5 7.2 48.2
Lower respiratory tract infectiicn with silary rales wheezing andlor
Splenomegaly
Hematemesis ~e~~te~aI pain Palm rash Paetechia of soft palate
of Measles Infection
Complication Otitis media Otitis extema Sinusitis Stomatitis Pneumonia Keratitis Urinary tract infection or T-wave changes on electrocardiogram Jaundice Acute phvchosis
8.8 5.2
2.6
3.5
5.3 0.9 0.9 5.2
98.2 5&I 7.7
I.8 21.0 12.3 3.5 30.7 15.4 7.7
2.6 7.7
0.9 0.9 8.9 1.8 15.4 0 7.7 7.7
in 461 Percent 9.8 6.5 4.1 3.9 3.7 3.3 1.5 0.7 0.4 0.2
=9
23.7 24.6 5.3
39.7 211.7 Il.7 10.4 7. 6.5 2.4 4.1 2.6 I.1 1.1 1.1 0.9
aI pain
le 3. Complications Young Adults
e phosphate Bilirubin CK Aklolase I
8
49.1 70.2 94.7
is iderltical to the rce recruits with
2116
JOURNAL OF ADOLESCENT HEALTH CARE Vol. 9, No. 3
LEIBOVICIET AL.
colnpared
to the rate
of 2.5% in U.S. Air Force re-
cruits (10). The rate of ECG zbnormalities (0.7% in our patients) was surprisingly low. Textbooks (19-23) and detailed reviews (2425) mention abnormal electrocardiograms in up to 20-30% of measles patients. The initial research was performed in hospitalized children (2627) or young adults (ll), groups selected for the severity of their disease. It may be that in unselected young adult measles patients, ECG abnormalities occur in less than 1% of patients. Abnormal liver enzymes have been described in 3~30% of measles patients (10,11,20,28), but these groups were either selected for severe illness or were too small to determine the true frequency. In our group, the percentage of patients with one or more high hepatic enzyme values was 51%, but only 0.4% of the patients were jaundiced, and in only 5.3% was the alkaline phosphatase elevated. Gavish et al. (11) reported a correlation between abnormal liverfunction tests and secondary bacterial infection. Both phenomena occurred from days 5 to 9 after the appearance of the rash. Was the rise in serum enzymes partly and nonspecifically caused by the pneumonia and not by measles? We were unable to demonstrate any correlation between abnormal liver enzymes on days l-2 after the appearance of the rash and subsequent complications. The single correlation between initial laboratory values and complications was the low total count of lymphocytes in patients with lceratitis. Leukopenia, lymphopenia, and abnormal liver enzymes on days l-2 after the appearance of the rash were otherwise not predictive of complications. The elevation of CK-MM and aldolase levels in our patients were well above the normal range. This in association with a normal EMG (n = 6) and a positive urine myoglobin in some of our patients is suggestive of ~~~bolomyo~ysis. lase values in measles patients (11). Although rhab in viral diseases (29,30), it has not been mentioned in previous descriptions of measles (g11, K-25). Twenty-five of our patients had been vaccinated in childhood. The clinical features of measles infection in these patients were identical to the r-rt of &le p. They did not differ in initial and convalescence measles hemagglutination inhibiting an& body titers. This fact may point to a primary failure of the vaccine (31). The duration of the protection afforded by childhood immunization had been questioned (32,33).
Summa y Measles infection in our group of healthy, well-nourished young adults caused milder complications and less severe morbidity than reported in some developing countries (1) or in Europe 50 years ago (34). Worthy of emphasis are our low rate of ECG abnormalities and possible rhabdomyolysis. Because such an epidemic pk. -‘es a heavy financial burden on institutions and systems such as an army or u versity, and because childhood immunization does not fully protect young adults agains we believe that a hint of a meas mands a search to indent@ suscep ther possible course, probabl immunization. safer but more nsive, is screening of all youn adults and immunization of susceptible ones on entering the specific institution.
References 1. Assaad F. Measles: Summary of worldwide impact. Rev Infect Dis 1983;5:452-9. 2. Hinman AR, Orenstein WA, Bloch AB, et al. Impact of measles in the United States. Rev Infect Dis 1983;5:439-44. 3. Miller CL. Current impact of measles in the United KinBdo~~ Rev Infect Dis 1983;5427-32. 4. Bryce La&e RR. Impact of measles in Canada. Rev Infect Dis 1983;5:445-51. 5. Roden AT, Heath WCC. Effects of vaccination against measles on the incidence of disease and immunity of the child population in England and Wales. Health Trends 1977;9:6972. 6. Rand KH, Emmons RW, Merigen TC. Measles in adults: An unforeseen consequence of immunization? JAMA 1976; 236z1028-31. 7. Cvjetanovic 6, Grab 6, Dixon H. Epidemiological models of poliomyelitis and measles and their application in the planning of immunization programs. Bull WHO 1982;68:485-22. 8. Editorial. Mathematics and Measles. Lancet 1982;2:148-9. 9. Amler RW, Orenstein WA. Measles in young adults. Postgrad Med 1985;77:251-61. 10. Gremilion DH, Crawford GE. Measles pneumonia in young adults: an analysis of 106 cases. Am J Med 1981;71:539-42. 11. Gavish D, Kleinman Y, Morag A, Chajek-Shaul T. Hepatitis and jaundice associated with measles in young adults. Arch Intern Med 1983;143:6747. 12. Israel Ministry of Health. Selected communicable diseases in Israel 1982. Monthly Epidemiological Bull 1983;18: 15-6. 13. Matzldn H, Regev S, Nili E. A measles outbreak in the Israel Defence Forces during the 1982 epidemic. Isr J Med Sci 1985;351-5. 14. SAS Institute Inc. SAS User’s Guide: Statistics, 1982 ed. Gary, NS: SAS Institute Inc., 1982. 15. SAS Institute Inc. SAS User’s Guide: Basics, 1982 ed. Gary, NSSAS Institute Inc., 1982. 16. Miller DL. Frequency of complications of measles, 1963. Br Med J 1964;2:75-8.
c CL.
17.
severityof no
red J 1978;P:
26.
1253. 18. 27. 28.
19.
ysfianctionin acutemeasles 1977;137:117&9.
20.
AL.
measles in-
29.
21.
22.
23.
31. 32. 33.
24. 34.
we
ofprotection by
aslesvaccine.J &&aR
Fmn the Israel Defence Forces Medical Corps (L.L., T.S., G.A.), the Depzrtmentof Pediatrics, Beilimson Medical Center, Petah Tiqva (G.A.) and the Departmmt of Cmmunify Health, Cannel Hospifal, Waifi, Israel (L.M.E.). rtment of Internal Medicine B BeiPrese& alyiriations: L. L.: rtment @Infernal linson Medical Cenlei-, i%t~h Tiqva, brae!; T.S.: Medicine, Rivfra Ziv Hospital, @at, Israel; O.K.: htilufe of PedkPric Endocrinology, Beilinson Medical Center, Petah Tiqva, Israel dress reprint requests to: L. Leikwici, M.D., Department oJMedicine B, Beilinson Medical Center, Petah Tiqva 49100, Israel. Manuscript accepted January 17, 1987.
Q society for Adolescent Medicine, 1988 Published by Elsevier Science Publishing Co., Inc., 52 Vanderbilt Ave., New York, NY 10017
LElBovIQ ET AL.
a standard form. Patients without complications were hospitalized until defervescence and fading of the rash on face and upper trunk. All patients were examined again 3 days after discharge and on additional occasions if clinically indicated. Chest roentgenographs were obtained in 195 patients who had abnormal findings on physical examinationof the lungs, and x-rays of the frontal and maxillary sinuses were taken in 112 patients with headache and/or purulent nasal discharge. Sinusitis was diagnosed if there was diffuse opacification or if an air-fluid level observed in a paranasal sinus. An electrocardiogram (RCG) was obtained in 172 randomly chosen patients on the first or second day after the appearance of the rash and again 4 to 5 days later. Patients who complained of an earache with some irritation of the tympanic membrane and auditory as having otitis externa, canal were diagnos whereas those with iteration of the light reflex and a red, bulging membrane were diagnosed as having otitis media. All patients with conjunctival injection were examined by slit lamp and fluorescein staining for evidence of keratitis. A total and differential cell count, erythrocyte sedimentation rate (ESR), and microscopic examination of urine sediment were performed in all patients on the first or second day after the appearance of the rash. Serum ghttamic oxaloacetic transaminase (SGOT), lactic creatine kinase (CK), total a alkaline phosphatase were obtained on the same day in 114 randomly chosen patients. The CK isoenzymes were quantified by immunoinhibition. We measured aldolase levels in the 13 patients with the highest serum CK, and an electromyography (EMG) was performed on six patients with a high CK and aldolase. Data about immunization were ascertained from childhood immunization cards. The data were stored and analyzed using the Statistical Analysis System (14,15). Statistical significance was tested by the x2 analysis for contingency tables, a two-tailed t-test for continuous variables with a normal distribution, and by a Wilcoxonnonparametric test for other continuous variables. The hypothesis that the values of a continuous variable were randomly Chosen from a normal distribution was tested by the Kohnogorov-Smirnov statistic or by the Shapiro-Wile statistic, as appropriate (15, p. 580). Thee e values are given as multiplications Of the normal range (i.e., 1 = within normal range;
JOURNAL OF ADOLESCENT HEALTH C
Vol. 9, No. 3
Table1. ClinicalFeatures of Measles Prodrome in Young Adults Clinical feature
Cough and coryza Fever (>37.5T) Conjuctivitis Photophobia Vomiting Abdominal pains Diarrhea
Pecentage of patients loo.0 97.8 47.7 26.9 7.8 4.6 4.6
Results
(range 17-26 yr). They
per high power field) in 2.5%. Although only two patients were jaundiced, 50.9% of the pati had elevated SGOT LDH, 29.8%; and a 4). The CK was eleva elevated fraction was mined. Traces of myog of 14% of patients with patients with the highest s, 12 had an elevated serum aldolase, but no a served in the six EMGs performed.
ASLES
Percent 1234567
Enanthem Cough and coryza Koplik’s spots Conjuctivitis I-Iemorrhagic conjunctivitis Cervical lym~~~enopat~y AxiIlary lymphadenopathy Inguinal lympha~eno~at~y
99.6 99.3 98.0 47.3 2.4 47.3 6.5 7.2 48.2
Lower respiratory tract infectiicn with silary rales wheezing andlor
Splenomegaly
Hematemesis ~e~~te~aI pain Palm rash Paetechia of soft palate
of Measles Infection
Complication Otitis media Otitis extema Sinusitis Stomatitis Pneumonia Keratitis Urinary tract infection or T-wave changes on electrocardiogram Jaundice Acute phvchosis
8.8 5.2
2.6
3.5
5.3 0.9 0.9 5.2
98.2 5&I 7.7
I.8 21.0 12.3 3.5 30.7 15.4 7.7
2.6 7.7
0.9 0.9 8.9 1.8 15.4 0 7.7 7.7
in 461 Percent 9.8 6.5 4.1 3.9 3.7 3.3 1.5 0.7 0.4 0.2
=9
23.7 24.6 5.3
39.7 211.7 Il.7 10.4 7. 6.5 2.4 4.1 2.6 I.1 1.1 1.1 0.9
aI pain
le 3. Complications Young Adults
e phosphate Bilirubin CK Aklolase I
8
49.1 70.2 94.7
is iderltical to the rce recruits with
2116
JOURNAL OF ADOLESCENT HEALTH CARE Vol. 9, No. 3
LEIBOVICIET AL.
colnpared
to the rate
of 2.5% in U.S. Air Force re-
cruits (10). The rate of ECG zbnormalities (0.7% in our patients) was surprisingly low. Textbooks (19-23) and detailed reviews (2425) mention abnormal electrocardiograms in up to 20-30% of measles patients. The initial research was performed in hospitalized children (2627) or young adults (ll), groups selected for the severity of their disease. It may be that in unselected young adult measles patients, ECG abnormalities occur in less than 1% of patients. Abnormal liver enzymes have been described in 3~30% of measles patients (10,11,20,28), but these groups were either selected for severe illness or were too small to determine the true frequency. In our group, the percentage of patients with one or more high hepatic enzyme values was 51%, but only 0.4% of the patients were jaundiced, and in only 5.3% was the alkaline phosphatase elevated. Gavish et al. (11) reported a correlation between abnormal liverfunction tests and secondary bacterial infection. Both phenomena occurred from days 5 to 9 after the appearance of the rash. Was the rise in serum enzymes partly and nonspecifically caused by the pneumonia and not by measles? We were unable to demonstrate any correlation between abnormal liver enzymes on days l-2 after the appearance of the rash and subsequent complications. The single correlation between initial laboratory values and complications was the low total count of lymphocytes in patients with lceratitis. Leukopenia, lymphopenia, and abnormal liver enzymes on days l-2 after the appearance of the rash were otherwise not predictive of complications. The elevation of CK-MM and aldolase levels in our patients were well above the normal range. This in association with a normal EMG (n = 6) and a positive urine myoglobin in some of our patients is suggestive of ~~~bolomyo~ysis. lase values in measles patients (11). Although rhab in viral diseases (29,30), it has not been mentioned in previous descriptions of measles (g11, K-25). Twenty-five of our patients had been vaccinated in childhood. The clinical features of measles infection in these patients were identical to the r-rt of &le p. They did not differ in initial and convalescence measles hemagglutination inhibiting an& body titers. This fact may point to a primary failure of the vaccine (31). The duration of the protection afforded by childhood immunization had been questioned (32,33).
Summa y Measles infection in our group of healthy, well-nourished young adults caused milder complications and less severe morbidity than reported in some developing countries (1) or in Europe 50 years ago (34). Worthy of emphasis are our low rate of ECG abnormalities and possible rhabdomyolysis. Because such an epidemic pk. -‘es a heavy financial burden on institutions and systems such as an army or u versity, and because childhood immunization does not fully protect young adults agains we believe that a hint of a meas mands a search to indent@ suscep ther possible course, probabl immunization. safer but more nsive, is screening of all youn adults and immunization of susceptible ones on entering the specific institution.
References 1. Assaad F. Measles: Summary of worldwide impact. Rev Infect Dis 1983;5:452-9. 2. Hinman AR, Orenstein WA, Bloch AB, et al. Impact of measles in the United States. Rev Infect Dis 1983;5:439-44. 3. Miller CL. Current impact of measles in the United KinBdo~~ Rev Infect Dis 1983;5427-32. 4. Bryce La&e RR. Impact of measles in Canada. Rev Infect Dis 1983;5:445-51. 5. Roden AT, Heath WCC. Effects of vaccination against measles on the incidence of disease and immunity of the child population in England and Wales. Health Trends 1977;9:6972. 6. Rand KH, Emmons RW, Merigen TC. Measles in adults: An unforeseen consequence of immunization? JAMA 1976; 236z1028-31. 7. Cvjetanovic 6, Grab 6, Dixon H. Epidemiological models of poliomyelitis and measles and their application in the planning of immunization programs. Bull WHO 1982;68:485-22. 8. Editorial. Mathematics and Measles. Lancet 1982;2:148-9. 9. Amler RW, Orenstein WA. Measles in young adults. Postgrad Med 1985;77:251-61. 10. Gremilion DH, Crawford GE. Measles pneumonia in young adults: an analysis of 106 cases. Am J Med 1981;71:539-42. 11. Gavish D, Kleinman Y, Morag A, Chajek-Shaul T. Hepatitis and jaundice associated with measles in young adults. Arch Intern Med 1983;143:6747. 12. Israel Ministry of Health. Selected communicable diseases in Israel 1982. Monthly Epidemiological Bull 1983;18: 15-6. 13. Matzldn H, Regev S, Nili E. A measles outbreak in the Israel Defence Forces during the 1982 epidemic. Isr J Med Sci 1985;351-5. 14. SAS Institute Inc. SAS User’s Guide: Statistics, 1982 ed. Gary, NS: SAS Institute Inc., 1982. 15. SAS Institute Inc. SAS User’s Guide: Basics, 1982 ed. Gary, NSSAS Institute Inc., 1982. 16. Miller DL. Frequency of complications of measles, 1963. Br Med J 1964;2:75-8.
c CL.
17.
severityof no
red J 1978;P:
26.
1253. 18. 27. 28.
19.
ysfianctionin acutemeasles 1977;137:117&9.
20.
AL.
measles in-
29.
21.
22.
23.
31. 32. 33.
24. 34.
we
ofprotection by
aslesvaccine.J &&aR