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Measles pneumonia in young adults
Measles Pneumonia in Young Adults An Analysis of 106 Cases
DAVID H. GREMILLION, U.S.A.F., MC. GEORGE E. CRAWFORD, U.S.A.F., MC. San Antonio, Texas
Measles occurred in 3,220 Air Force recruits between January 1976 and July 1979 and was complicated by pneumonia in 106 cases (3.3 percent). Although no deaths occurred, the illness was characterized as clinically severe with high fever and prolonged hospitalization (mean, 14.5 days). Bacterial superinfection as documented by transtracheal aspiration occurred in 35 cases (30.3 percent) and was caused by Hemophilus influenzae (16), Hemophilus parainfluenzae (two), Neisseria meningitidis (nine), Streptococcus pneumoniae (three), Streptococcus pyogenes (two) and Moraxella kingae (one). Clinical evidence of bronchospasm was present in 16 patients (17 percent) and required bronchodilators in six. Other complications included liver function abnormalities (31 percent), otitis media (29 percent) and sinusitis (25 percent). Measles pneumonia in adolescents is clinically severe with a generally benign outcome. Although measles is traditionally a childhood illness, recent reports have emphasized increasing frequency in adolescents and young adults [ 1,2]. These large outbreaks in this older age group in general and Air Force recruits in particular [3] have suggested that the incidence and clinical features of complications, including pulmonary, are somewhat different from these reflected in the traditional literature, which deals largely with children [4]. Previous reports have characterized measles pneumonia as common in the pediatric age group with serious consequences. These traditional views require reassessment in the young adult. A large epidemic of measles in USAF recruits at Lackland AFB, Texas, has provided a unique opportunity to study measles pneumonia. MATERIALS AND METHODS Patient Population. An epidemic of 3,220 cases of clinical measles occurred
From the Infectious Disease Service, Wilford Hall, United States Air Force Medical Center, Lackland Air Force Base, San Antonio, Texas. Requests for reprints should be addressed to Dr. David H. Gremillion, WHMCEGHMMI, Lackland Air Force Base, San Antonio, TX 78236. Manuscript accepted May 28, 1981.
in Air Force recuits at Lackland AFB from January 1976 to July 1979. In March 1979, measles immunization of susceptible recuits was instituted. Since that time, measles has ceased to occur in this population. The diagnosis of measles was made on clinical criteria and substantiated in a subgroup by means of paired serologic studies. Hemagglutination inhibition titers were determined during the acute phase and one to four weeks later. Patients with measles pneumonia were hospitalized at Wilford Hall USAF Medical Center and seen by a member of the Infectious Disease staff. Patients with complicating pneumonia were found by reviewing discharge diagnoses from January 1976 to July 1979 for those with a diagnosis of measles and pneumonia. These cases were reviewed and included in the study if there was evidence of measles based on a typical rash, conjunctivitis or Koplik’s spots and evidence of pneumonia based on the presence of cough, fever and roentgenographic changes.
October 1981
The American Journal of Medicine
Volume 71
539
MEASLES
PNEUMONIA
IN YOUNG ADULTS-GREMILLION,
TABLE I
CRAWFORD
Radiographic
Findings in Patients With Measles Pneumonia
Measles Pneumonia (71) Lobar consolidation Interstitial Multilobar Lower lobe
Upper lobe Nodular Pleural effusion l
Radioaraohs
Measles Pneumonia with Superinfection’(35)
5 (7.0%) 60 (84.5%) 27 (38.0)
3 (8.6%) 32 (91.4%) 24 (68.6%) 29 (82.9%) 7 (20.0%) 2 (5.7%) 2 (2.8%)
37 (52.1%) 20 (28.6%) 3 (4.2%) 2 (2.8%)
taken after bacterial
infection
P Value7 NS NS
0.004 0.0026 NS NS NS
documented.
+ Fisher’s exact text. Bacteriologic Studies. When bacterial superinfection was suspected on the basis of clinical toxicity, recrudescent fever or leukocytosis, patients underwent transtracheal aspiration. The samples obtained were immediately Gram-stained and inoculated on blood, chocolate and MacConkey agar at the bedside. The remainder of each specimen was injected into gassed out vials and transported into the laboratory for anaerobic culture. Aerobic isolates were identified by standard methods. Anaerobic isolates were identified in accordance with the criteria of the Virginia Polytechnic Institute. RESULTS Between January 1976 and July 1979,3,220 cases of measles occurred at Lackland AFB predominantly in military recruits. Pneumonia was diagnosed in 106 cases (3.3 percent). Serologic Findings. Paired serum samples were available in a subgroup of 68 patients. Forty-two (62 percent) showed a four-fold or greater rise in hemagglutination titers to measles virus. Demographic Characteristics. Of the 106 patients with pneumonia complicating measles, 96 were male and 10 were female. Age range was 17 to 26, with a mean of 18.9 years. This age corresponds to the average age of military recruits, and the sex distribution is similar to that in the recruit population. Radiographic Findings. The radiographic presentation of measles pneumonia is summarized in Table I. A fine reticulonodular infiltrate was the most common finding, accounting for 87 percent of cases. Infiltrates were commonly multilobar, with the lower lobes predominating. Pleural effusion, lobar consolidation and nodular infiltrates were uncommon, with the latter occurring predominantly in patients with the atypical measles syndrome. Radiographic findings in patients with bacterial superinfection were generally similar. Even though multilobar and lower lobe findings were more prevalent in the group with superinfection, these findings were not useful clinically. Physical Findings. Physical findings included a maculopapular rash in all cases, with an atypical appearance and progression in four cases. Atypical measles was diagnosed when the rash first appeared on the extremities and spread inward to involve the trunk.
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The American Journal of Medicine
Koplik’s enanthem was present in 71 (67 percent). Pulmonary findings included rales on auscultation in 90 (85 percent) and wheezing in 18 (17 percent). Oral temperatures were over 102’F in 94 percent of cases and over 104’F in 42 percent. Complications Other Than Pulmonary. Complications other than pulmonary were common in patients with measles pneumonia with or without bacterial superinfection. These included liver function abnormalities (31 percent), otitis media (29 percent) and sinusitis (25 percent). Seven patients acquired measles during hospitalization for another unrelated illness. Laboratory Findings. Abnormal liver function test results were present in 33 cases (31 percent), and consisted mainly of mild elevations of serum glutamic oxaloacetic transaminase and lactic dehydrogenase. Complete blood cell counts in patients without superinfection demonstrated a mean white blood cell count of 8,400/mm3 with a predominant left shift (over 10 percent band forms) in 20 percent, as compared with those in patients with bacterial infection who had a mean white blood cell count of 12,l 00/mm3 and a left shift in 55 percent. Arterial blood gases were obtained in 24 patients with bacterial pneumonia with a mean Pop on room air of 62.2 mm Hg. Microbiologic Findings. Transtracheal aspiration was performed in 40 patients when signs of bacterial superinfection were detected. These findings generally occurred between the fifth and tenth days after onset of the rash (mean 6.3 days). There were no complications of transtracheal aspiration. No organisms were recovered in five specimens, leaving 35 bacterial superinfections proved by transtracheal aspiration. The predominant pathogen was H. influenzae (in 18), with N. meningitidis (in nine; GP Y in six, GP X in one, GP B in one, and GP A in one), Strep. pneumoniae (in three), Strep. pyogenes (in two), H. parainfluenzae (in two) and M. kingae (in one) somewhat less common. All H. influenzae isolates were nontypable and beta-lactamase-negative. Sputum cultures in an additional six patients revealed H. influenzae in three and Strep. pneumoniae in three. The value of sputum Gram-stain in predicting the causative pathogen was assessed in
Volume 71
MEASLES
PNEUMONIA
IN YOUNG ADULTS-GREMILLION,
CRAWFORD
34 patients, Sputum Gram-stain examination predicted the correct pathogen in only 13 patients with bacterial pneumonia and was misleading in the remaining 2 1.
earlier study. He speculated on a natural diminution in measles virulence since 1927. Only 3 percent of the patients in Snell’s series were older than eight years.
Treatment.
In separate studies, Weinstein [ 13,141 found rates of 12.2 percent and 25.2 percent, respectively. In all reported cases, the patient was younger than 10 years of age, with most under five. In a revealing study published in 1930, Kohn and Koiransky [ 151 performed sequential chest x-rays in the pre-eruptive and post-eruptive phases of acute measles in 130 patients. They found a remarkable 49 percent of patients with pulmonary infiltrates occurring during the pre-eruptive or eruptive phase and an additional 8 percent occurring during the post-eruptive phase. Few studies have assessed the frequency of pneumonia complicating measles in young adults. In a group of naval recruits, Olson et al. [9] found that pulmonary complications developed in 16 of 32 (50 percent) patients with measles. Chest x-rays were performed on all patients, specifically seeking pulmonary complications. In the present study, evidence of pneumonia as diagnosed by chest x-ray and clinical findings was present in 3.3 percent with clinically diagnosed measles. Chest x-rays were performed only in those patients in whom pulmonary complications were clinically suggested, thus the true incidence of pneumonia may have been underestimated. Radiographic findings were not distinctive, with interstitial and multilobar infiltrates most common and a conspicuous rarity of pleural effusions. Patients with bacterial superinfections were more likely to have multilobar and lower lobe infiltrates than were those without superinfection, but this was not a clinically useful observation. These findings are consistent with those of other observers. Weinstein and Franklin [ 141 noted predominantly patchy infiltration and mild peribronchial infiltration. In Kohn and Koiransky’s study [ 161, pulmonary infiltrates tended to appear and regress with the activity of the rash in 90 percent of cases. Pleural effusions were present in only 7 percent in their series. Likewise in Weinstein’s study [ 131, the pulmonary and cutaneous findings followed a parallel course in 83 percent. Enlargement of hilar nodes has been prominent among the findings of other investigators, with 60.3 percent in Fawcitt and Parry’s series [ 1 l] and 27 percent in Kohn and Koiransky’s series [ 161. Hilar adenopathy may be more common in patients with the atypical measles syndrome. All 10 patients had enlargement of hilar nodes in the series of Young et al. [ 171, as did three of seven in the series of Martin et al. [ 181. DeCarlo and Startzman [ 191 noted a 37 percent incidence of hilar adenopathy in a group of 60 patients with measles pneumonia: in half of these, no concurrent pulmonary infiltrate was found. In our study, hilar adenopathy was encountered only in those patients with the atypical measles syndrome. Nodular parenchymal le-
Treatment with antibiotics was instituted in 78 patients (74 percent). Antibiotic administration was often started empirically and stopped or changed when microbiologic information became available. Ampicillin (46), penicillin G (21) and methicillin (eight) were the most commonly employed antibiotics. Other antibiotics used on one occasion each included chloramphenicol, erythromycin and trimethoprim-sulfamethoxazole. Hospital stay was substantially prolonged to 14.5 f 5 days in those with pneumonia, compared with 3.6 days in those without pneumonia. Bronchodilators were used in six patients in whom the clinical picture was dominated by wheezing. COMMENTS Pneumonia is often a serious complication of measles, accounting for 60.1 percent of 1,283 reported deaths due to measles in the U.S. between 1964 and 1971 [5]. Mortality with pneumonia, as with other measles complications, increases with malnutrition and young age [6,7]. Escobar et al. [7] noted a mortality of 10.5 percent in 38 cases of measles pneumonia among patients in Cali, Colombia. Mortality increased from 3.8 percent in those with normal nutritional status to 21 percent in those with moderate malnutrition. Data collected in developing countries suggest that nutritional status is an important factor in mortality rates [ 81. Age may also be an important factor, with 76 percent of deaths in Barkin’s series occurring in patients younger than four years [5]. Barkin noted a progressive decline in case fatality ratio that continued through adolescence. Escobar et al. likewise recorded highest mortality rates for patients under age four. In previously healthy adolescents, however, pneumonia appears to be a relatively benign complication, accounting for no deaths in series of 32 cases reported by Olson et al. [9] and no deaths in our series of 106 cases. Many patients in our series were moderately ill, however, as evidenced by prolonged hospitalization compared with those without pneumonia. Although pneumonia is regarded as a common complication of measles, its frequency appears to be highly variable. Rates of 3.5 percent to 50 percent have been reported by different authors [ 10,111. These reported incidences may reflect the bias induced by certain host factors such as age and nutritional status, as well as the care with which pneumonia was sought in each case. Snell [ 121 compared the incidence of pneumonia in England in studies conducted in 1927-28 (27.4 percent) with a similar study conducted by Miller in 1963 (3.8 percent). The seven-fold reduction in pneumonia was attributed to poor social conditions and the lack of availability of antibiotics at the time of the
October 1981
The American Journal of Medicine
Volume 71
541
MEASLES
PNEUMONIA IN YOUNG ADULTS-GREMILLION,
CRAWFORD
sions have also been commonly reported in patients with the atypical measles syndrome [20]. Four of the five patients with nodular lesions iti our study were patients with the atypical syndrome. These nodular lesions may persist for six to 22 months [ 171. The major importance of this finding is to differentiate these residua from those lesions requiring invasive diagnostic procedures. Bacterial superinfection was detected in one-third of our cases, most often five to 10 days after the onset of rash. A deteriorating clinical and pulmonary status with a resolving rash was an early hint of bacterial superinfection. Clinical deterioration was often present with higher fever, elevated white blood cell count and purulent sputum production. The frequent identification of l-f. influenzae and N. meningitidis is not surprising in that prior reports dealing with superinfection of viral pneumonia in Air Force recruits reflect similar pathogens [21,22]. Likewise, in a group of Navy recruits with measles and a complicating bacterial pneumonia, Olson et al. [9] identified N. meningitidis in 60 percent of cases but found H. influenzae infrequently. In a classic study of bacterial complications in measles, Weinstein and Franklin [ 141 noted the frequent (38 percent) occurrence of H. influenzae, but recorded no cases of N. meningitidis. The latter may therefore be more characteristic of closed populations as in military recruit training centers. The occurrence of Staph. aureus and Strep. pyogenes has been emphasized in other reports [23]. No case of Staph. aureus and only two of Strep. pyogenes were encountered in the present study. Therapy with ampicillin or penicillin was instituted in
most cases and usually resulted in prompt improvement. It is of interest that in Olson’s study, 20 percent of patients with bacterial pneumonia proved by transtracheal aspiration had improvement without antibiotics. We have found transtracheal aspiration to be indispensable in the microbiologic diagnosis of measles pneumonia with bacterial superinfection. This technique is safe and offers a high diagnostic yield. Measles pneumonia is herein shown to be a clinically severe illness in young adults, with high fever, toxic appearance and significantly prolonged hospitalization. Unlike children and compromised hosts, however, adolescents and young adults tolerate the illness well and deaths are rare. Radiographic features are insufficient to differentiate other nonbacterial pneumonias, with the exception of the atypical measles syndrome, which has characteristic findings. Pulmonary hilar adenopathy and nodular pulmonary infiltrates in a young adult should prompt the physician to question the patient carefully for a history of recent measles to avoid unnecessary invasive diagnostic procedures. Outbreaks of measles and its attendant complications may be expected to continue in adolescents in the unimmunized civilian community. Internists as well as pediatricians should
therefore maintain familiarity common sequelae.
with measles and its
ACKNOWLEDGMENT We gratefully acknowledge forming serologic studies secretarial assistance.
Dr. Harsty Dupuy for perand Kathleen Cannon for
REFERENCES
2.
3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.
542
Krause PJ, Cherry JD, Deseda-Tous J, et al.: Epidemic measles in young adults. Ann Intern Med 1979; 90: 873-76. Rand KH, Emmons RW, Merigan TC: Measles in adults. An unforeseen consequence of immunization? JAMA 1976; 236: 1028-1031. Crawford GE, Gremillion DH, Martinez V: Measles in Air Force recruits-Texas. MMWR 1979; 28: 46. Gremillion DH: Pulmonary complications in measles patients. J Respir Dis 1980; 2: 76-87. Barkin RM: Measles mortality: a retrospective look at the vaccine era. Am J Epidemiol 1975; 102(4): 341-349. Ghost S, Dhatt PS: Complications of measles. Indian J Child Health 1961; 10: 111. Escobar JA, et al.: Etiology of respiratory tract infections in children in Cali, Colombia. Pediatrics 1976; 57: 123. Morley DC, Martin WJ, Allen I: Measles in West Africa. West Afr Med J 1967; 16: 24-31. Olson RW, et al.: Measles pneumonia: bacterial suprainfection as a complicating factor. JAMA 1975; 232: 363-365. Miller DL: Frequency of complications of measles, 1963. Br Med J 1964: 2: 75-78. Fawcitt J, Parry HE: Lung changes in pertussis and measles in childhood. Br J Radio1 1957; 30: 76-82. Snell WE: Measles and its complications 50 years ago. Public Health 1976; 90: 211-217. Weinstein L: Failure of chemotherapy to prevent the bacterial complications of measles. N Engl J Med 1955; 253:
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14. 15.
16. 17. 18.
19. 20.
21.
22.
23.
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679-683. Weinstein L, Franklin W: Pneumonia of measles. Am J Med Sci 1949; 217: 314-324. Kohn JL, Koiransky H: Roentgenographic re-examination of the chests of children six to ten months after measles. Am J Dis Child 1931; 41: 500-506. Kohn JL, Koiransky H: Roentgenographic examination of the chest in measles. Am J Dis Child 1929; 38: 258. Young LW, Smith DL, Glascow LA: Pneumonia of atypical measles. Am J Roentgen01 1970; 110: 439-447. Martin DB, Weiner LB, Neiburs PI. et al.: Atypical measles in adolescents and young adults. Ann Intern Med 1979; 90: 877-881. DeCarlo J, Startzman HH: The roentgen study of the chest in measles. Radiology 1954; 63: 849-852. Greenfield H, Gyepes MT: Oval shaped consolidations simulating new growth of lung. Am J Roentgen01 1964; 91: 125-131. Geckler R, Gremillion DH, McAllister K, Ellenbogen C: Microscopic and bacteriologic comparison of paired sputa and transtracheal aspirate. J Clin Microbial 1977; 6: 396-399. Koppes G, Gebhart RJ, Ellenbogen C: Neisseria meningitidis group Y pneumonia in Air Force recruits. Am J Med 1977; 62: 66 l-666. Dover AS, Escobar JA, Duenas AL, Leal EC: Pneumonia associated with measles. JAMA 1975; 234: 612-614.
DAVID H. GREMILLION, U.S.A.F., MC. GEORGE E. CRAWFORD, U.S.A.F., MC. San Antonio, Texas
Measles occurred in 3,220 Air Force recruits between January 1976 and July 1979 and was complicated by pneumonia in 106 cases (3.3 percent). Although no deaths occurred, the illness was characterized as clinically severe with high fever and prolonged hospitalization (mean, 14.5 days). Bacterial superinfection as documented by transtracheal aspiration occurred in 35 cases (30.3 percent) and was caused by Hemophilus influenzae (16), Hemophilus parainfluenzae (two), Neisseria meningitidis (nine), Streptococcus pneumoniae (three), Streptococcus pyogenes (two) and Moraxella kingae (one). Clinical evidence of bronchospasm was present in 16 patients (17 percent) and required bronchodilators in six. Other complications included liver function abnormalities (31 percent), otitis media (29 percent) and sinusitis (25 percent). Measles pneumonia in adolescents is clinically severe with a generally benign outcome. Although measles is traditionally a childhood illness, recent reports have emphasized increasing frequency in adolescents and young adults [ 1,2]. These large outbreaks in this older age group in general and Air Force recruits in particular [3] have suggested that the incidence and clinical features of complications, including pulmonary, are somewhat different from these reflected in the traditional literature, which deals largely with children [4]. Previous reports have characterized measles pneumonia as common in the pediatric age group with serious consequences. These traditional views require reassessment in the young adult. A large epidemic of measles in USAF recruits at Lackland AFB, Texas, has provided a unique opportunity to study measles pneumonia. MATERIALS AND METHODS Patient Population. An epidemic of 3,220 cases of clinical measles occurred
From the Infectious Disease Service, Wilford Hall, United States Air Force Medical Center, Lackland Air Force Base, San Antonio, Texas. Requests for reprints should be addressed to Dr. David H. Gremillion, WHMCEGHMMI, Lackland Air Force Base, San Antonio, TX 78236. Manuscript accepted May 28, 1981.
in Air Force recuits at Lackland AFB from January 1976 to July 1979. In March 1979, measles immunization of susceptible recuits was instituted. Since that time, measles has ceased to occur in this population. The diagnosis of measles was made on clinical criteria and substantiated in a subgroup by means of paired serologic studies. Hemagglutination inhibition titers were determined during the acute phase and one to four weeks later. Patients with measles pneumonia were hospitalized at Wilford Hall USAF Medical Center and seen by a member of the Infectious Disease staff. Patients with complicating pneumonia were found by reviewing discharge diagnoses from January 1976 to July 1979 for those with a diagnosis of measles and pneumonia. These cases were reviewed and included in the study if there was evidence of measles based on a typical rash, conjunctivitis or Koplik’s spots and evidence of pneumonia based on the presence of cough, fever and roentgenographic changes.
October 1981
The American Journal of Medicine
Volume 71
539
MEASLES
PNEUMONIA
IN YOUNG ADULTS-GREMILLION,
TABLE I
CRAWFORD
Radiographic
Findings in Patients With Measles Pneumonia
Measles Pneumonia (71) Lobar consolidation Interstitial Multilobar Lower lobe
Upper lobe Nodular Pleural effusion l
Radioaraohs
Measles Pneumonia with Superinfection’(35)
5 (7.0%) 60 (84.5%) 27 (38.0)
3 (8.6%) 32 (91.4%) 24 (68.6%) 29 (82.9%) 7 (20.0%) 2 (5.7%) 2 (2.8%)
37 (52.1%) 20 (28.6%) 3 (4.2%) 2 (2.8%)
taken after bacterial
infection
P Value7 NS NS
0.004 0.0026 NS NS NS
documented.
+ Fisher’s exact text. Bacteriologic Studies. When bacterial superinfection was suspected on the basis of clinical toxicity, recrudescent fever or leukocytosis, patients underwent transtracheal aspiration. The samples obtained were immediately Gram-stained and inoculated on blood, chocolate and MacConkey agar at the bedside. The remainder of each specimen was injected into gassed out vials and transported into the laboratory for anaerobic culture. Aerobic isolates were identified by standard methods. Anaerobic isolates were identified in accordance with the criteria of the Virginia Polytechnic Institute. RESULTS Between January 1976 and July 1979,3,220 cases of measles occurred at Lackland AFB predominantly in military recruits. Pneumonia was diagnosed in 106 cases (3.3 percent). Serologic Findings. Paired serum samples were available in a subgroup of 68 patients. Forty-two (62 percent) showed a four-fold or greater rise in hemagglutination titers to measles virus. Demographic Characteristics. Of the 106 patients with pneumonia complicating measles, 96 were male and 10 were female. Age range was 17 to 26, with a mean of 18.9 years. This age corresponds to the average age of military recruits, and the sex distribution is similar to that in the recruit population. Radiographic Findings. The radiographic presentation of measles pneumonia is summarized in Table I. A fine reticulonodular infiltrate was the most common finding, accounting for 87 percent of cases. Infiltrates were commonly multilobar, with the lower lobes predominating. Pleural effusion, lobar consolidation and nodular infiltrates were uncommon, with the latter occurring predominantly in patients with the atypical measles syndrome. Radiographic findings in patients with bacterial superinfection were generally similar. Even though multilobar and lower lobe findings were more prevalent in the group with superinfection, these findings were not useful clinically. Physical Findings. Physical findings included a maculopapular rash in all cases, with an atypical appearance and progression in four cases. Atypical measles was diagnosed when the rash first appeared on the extremities and spread inward to involve the trunk.
540
October 1981
The American Journal of Medicine
Koplik’s enanthem was present in 71 (67 percent). Pulmonary findings included rales on auscultation in 90 (85 percent) and wheezing in 18 (17 percent). Oral temperatures were over 102’F in 94 percent of cases and over 104’F in 42 percent. Complications Other Than Pulmonary. Complications other than pulmonary were common in patients with measles pneumonia with or without bacterial superinfection. These included liver function abnormalities (31 percent), otitis media (29 percent) and sinusitis (25 percent). Seven patients acquired measles during hospitalization for another unrelated illness. Laboratory Findings. Abnormal liver function test results were present in 33 cases (31 percent), and consisted mainly of mild elevations of serum glutamic oxaloacetic transaminase and lactic dehydrogenase. Complete blood cell counts in patients without superinfection demonstrated a mean white blood cell count of 8,400/mm3 with a predominant left shift (over 10 percent band forms) in 20 percent, as compared with those in patients with bacterial infection who had a mean white blood cell count of 12,l 00/mm3 and a left shift in 55 percent. Arterial blood gases were obtained in 24 patients with bacterial pneumonia with a mean Pop on room air of 62.2 mm Hg. Microbiologic Findings. Transtracheal aspiration was performed in 40 patients when signs of bacterial superinfection were detected. These findings generally occurred between the fifth and tenth days after onset of the rash (mean 6.3 days). There were no complications of transtracheal aspiration. No organisms were recovered in five specimens, leaving 35 bacterial superinfections proved by transtracheal aspiration. The predominant pathogen was H. influenzae (in 18), with N. meningitidis (in nine; GP Y in six, GP X in one, GP B in one, and GP A in one), Strep. pneumoniae (in three), Strep. pyogenes (in two), H. parainfluenzae (in two) and M. kingae (in one) somewhat less common. All H. influenzae isolates were nontypable and beta-lactamase-negative. Sputum cultures in an additional six patients revealed H. influenzae in three and Strep. pneumoniae in three. The value of sputum Gram-stain in predicting the causative pathogen was assessed in
Volume 71
MEASLES
PNEUMONIA
IN YOUNG ADULTS-GREMILLION,
CRAWFORD
34 patients, Sputum Gram-stain examination predicted the correct pathogen in only 13 patients with bacterial pneumonia and was misleading in the remaining 2 1.
earlier study. He speculated on a natural diminution in measles virulence since 1927. Only 3 percent of the patients in Snell’s series were older than eight years.
Treatment.
In separate studies, Weinstein [ 13,141 found rates of 12.2 percent and 25.2 percent, respectively. In all reported cases, the patient was younger than 10 years of age, with most under five. In a revealing study published in 1930, Kohn and Koiransky [ 151 performed sequential chest x-rays in the pre-eruptive and post-eruptive phases of acute measles in 130 patients. They found a remarkable 49 percent of patients with pulmonary infiltrates occurring during the pre-eruptive or eruptive phase and an additional 8 percent occurring during the post-eruptive phase. Few studies have assessed the frequency of pneumonia complicating measles in young adults. In a group of naval recruits, Olson et al. [9] found that pulmonary complications developed in 16 of 32 (50 percent) patients with measles. Chest x-rays were performed on all patients, specifically seeking pulmonary complications. In the present study, evidence of pneumonia as diagnosed by chest x-ray and clinical findings was present in 3.3 percent with clinically diagnosed measles. Chest x-rays were performed only in those patients in whom pulmonary complications were clinically suggested, thus the true incidence of pneumonia may have been underestimated. Radiographic findings were not distinctive, with interstitial and multilobar infiltrates most common and a conspicuous rarity of pleural effusions. Patients with bacterial superinfections were more likely to have multilobar and lower lobe infiltrates than were those without superinfection, but this was not a clinically useful observation. These findings are consistent with those of other observers. Weinstein and Franklin [ 141 noted predominantly patchy infiltration and mild peribronchial infiltration. In Kohn and Koiransky’s study [ 161, pulmonary infiltrates tended to appear and regress with the activity of the rash in 90 percent of cases. Pleural effusions were present in only 7 percent in their series. Likewise in Weinstein’s study [ 131, the pulmonary and cutaneous findings followed a parallel course in 83 percent. Enlargement of hilar nodes has been prominent among the findings of other investigators, with 60.3 percent in Fawcitt and Parry’s series [ 1 l] and 27 percent in Kohn and Koiransky’s series [ 161. Hilar adenopathy may be more common in patients with the atypical measles syndrome. All 10 patients had enlargement of hilar nodes in the series of Young et al. [ 171, as did three of seven in the series of Martin et al. [ 181. DeCarlo and Startzman [ 191 noted a 37 percent incidence of hilar adenopathy in a group of 60 patients with measles pneumonia: in half of these, no concurrent pulmonary infiltrate was found. In our study, hilar adenopathy was encountered only in those patients with the atypical measles syndrome. Nodular parenchymal le-
Treatment with antibiotics was instituted in 78 patients (74 percent). Antibiotic administration was often started empirically and stopped or changed when microbiologic information became available. Ampicillin (46), penicillin G (21) and methicillin (eight) were the most commonly employed antibiotics. Other antibiotics used on one occasion each included chloramphenicol, erythromycin and trimethoprim-sulfamethoxazole. Hospital stay was substantially prolonged to 14.5 f 5 days in those with pneumonia, compared with 3.6 days in those without pneumonia. Bronchodilators were used in six patients in whom the clinical picture was dominated by wheezing. COMMENTS Pneumonia is often a serious complication of measles, accounting for 60.1 percent of 1,283 reported deaths due to measles in the U.S. between 1964 and 1971 [5]. Mortality with pneumonia, as with other measles complications, increases with malnutrition and young age [6,7]. Escobar et al. [7] noted a mortality of 10.5 percent in 38 cases of measles pneumonia among patients in Cali, Colombia. Mortality increased from 3.8 percent in those with normal nutritional status to 21 percent in those with moderate malnutrition. Data collected in developing countries suggest that nutritional status is an important factor in mortality rates [ 81. Age may also be an important factor, with 76 percent of deaths in Barkin’s series occurring in patients younger than four years [5]. Barkin noted a progressive decline in case fatality ratio that continued through adolescence. Escobar et al. likewise recorded highest mortality rates for patients under age four. In previously healthy adolescents, however, pneumonia appears to be a relatively benign complication, accounting for no deaths in series of 32 cases reported by Olson et al. [9] and no deaths in our series of 106 cases. Many patients in our series were moderately ill, however, as evidenced by prolonged hospitalization compared with those without pneumonia. Although pneumonia is regarded as a common complication of measles, its frequency appears to be highly variable. Rates of 3.5 percent to 50 percent have been reported by different authors [ 10,111. These reported incidences may reflect the bias induced by certain host factors such as age and nutritional status, as well as the care with which pneumonia was sought in each case. Snell [ 121 compared the incidence of pneumonia in England in studies conducted in 1927-28 (27.4 percent) with a similar study conducted by Miller in 1963 (3.8 percent). The seven-fold reduction in pneumonia was attributed to poor social conditions and the lack of availability of antibiotics at the time of the
October 1981
The American Journal of Medicine
Volume 71
541
MEASLES
PNEUMONIA IN YOUNG ADULTS-GREMILLION,
CRAWFORD
sions have also been commonly reported in patients with the atypical measles syndrome [20]. Four of the five patients with nodular lesions iti our study were patients with the atypical syndrome. These nodular lesions may persist for six to 22 months [ 171. The major importance of this finding is to differentiate these residua from those lesions requiring invasive diagnostic procedures. Bacterial superinfection was detected in one-third of our cases, most often five to 10 days after the onset of rash. A deteriorating clinical and pulmonary status with a resolving rash was an early hint of bacterial superinfection. Clinical deterioration was often present with higher fever, elevated white blood cell count and purulent sputum production. The frequent identification of l-f. influenzae and N. meningitidis is not surprising in that prior reports dealing with superinfection of viral pneumonia in Air Force recruits reflect similar pathogens [21,22]. Likewise, in a group of Navy recruits with measles and a complicating bacterial pneumonia, Olson et al. [9] identified N. meningitidis in 60 percent of cases but found H. influenzae infrequently. In a classic study of bacterial complications in measles, Weinstein and Franklin [ 141 noted the frequent (38 percent) occurrence of H. influenzae, but recorded no cases of N. meningitidis. The latter may therefore be more characteristic of closed populations as in military recruit training centers. The occurrence of Staph. aureus and Strep. pyogenes has been emphasized in other reports [23]. No case of Staph. aureus and only two of Strep. pyogenes were encountered in the present study. Therapy with ampicillin or penicillin was instituted in
most cases and usually resulted in prompt improvement. It is of interest that in Olson’s study, 20 percent of patients with bacterial pneumonia proved by transtracheal aspiration had improvement without antibiotics. We have found transtracheal aspiration to be indispensable in the microbiologic diagnosis of measles pneumonia with bacterial superinfection. This technique is safe and offers a high diagnostic yield. Measles pneumonia is herein shown to be a clinically severe illness in young adults, with high fever, toxic appearance and significantly prolonged hospitalization. Unlike children and compromised hosts, however, adolescents and young adults tolerate the illness well and deaths are rare. Radiographic features are insufficient to differentiate other nonbacterial pneumonias, with the exception of the atypical measles syndrome, which has characteristic findings. Pulmonary hilar adenopathy and nodular pulmonary infiltrates in a young adult should prompt the physician to question the patient carefully for a history of recent measles to avoid unnecessary invasive diagnostic procedures. Outbreaks of measles and its attendant complications may be expected to continue in adolescents in the unimmunized civilian community. Internists as well as pediatricians should
therefore maintain familiarity common sequelae.
with measles and its
ACKNOWLEDGMENT We gratefully acknowledge forming serologic studies secretarial assistance.
Dr. Harsty Dupuy for perand Kathleen Cannon for
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