Bordetella Recent
Experience
parapertussis
and
Calvin C. Linnemann, Jr, MD,
a
Evelyn
Review of the Literature B.
Perry
\s=b\ During 1974, eight of 37 (22%) Bordetella organisms isolated from patients in Cincinnati were Bordetella parapertussis. This is in contrast to other experience in the United States where parapertussis has comprised < 5% of the Bordetella species isolated and suggests that B parapertussis infection may be more common in this country than generally recognized. The failure to appreciate the presence of this infection may result from the lack of cultures taken from children with mild disease and the failure to distinguish B
the
of Bordetella species dis¬ and capable of tinct from producing human disease, clinical ex¬ perience has suggested that this organism is a rare cause of mild pertussis.1·- In the United States and parapertussis has been Europe, reported as a cause of 5% or less of documented Bordetella infections.3-4 However, some European studies have suggested that this organism causes 20% to 30% of cases of pertussis syndrome, and may be more prevalent than pertussis.'-7 Although most reported cases of parapertussis
recognition Sinceparapertussis pertussis as
a
From the Infectious Disease Division, University of Cincinnati College of Medicine, and the Children's Hospital Medical Center, Cincinnati. Reprint requests to Infectious Disease Division, University of Cincinnati College of Medicine, 231 Bethesda Ave, Cincinnati, Ohio 45267
(Dr Linnemann).
parapertussis from
B pertussis. Cultures obtained from family members of three of the children with B parapertussis, and B pertussis was isolated from members of two families, including the mother and sister of a child who died of pneumonia and encephalopathy. These cases suggest that patients with severe disease associated with B parapertussis should be carefully evaluated for the possibility of dual infection caused by B pertussis. (Am J Dis Child 131:560-563, 1977) were
have been
mild, two cases of fatal pneumonia have been reported, which raises the question of whether the organism may cause severe disease.8
There are several reasons for the differences among the various stud¬ ies. Some of the studies represent experience over many years, whereas others report short-term surveys. True differences in prevalence among countries, failure to obtain cultures from patients with mild pertussis, and failure to distinguish the two orga¬ nisms may also account for some of these discrepancies. In the spring of 1974, an epidemic of
pertussis involving hospital personnel
occurred in Cincinnati." Because of this epidemic, pediatricians were alerted to culture all patients with paroxysmal coughs for pertussis. Dur¬ ing that year, 22% of Bordetella organisms isolated were paraper-
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tussis, including one from an infant who died of pneumonia and encepha¬ lopathy. This study reports the epi¬ demiologica! and clinical features of the patients with parapertussis. MATERIALS AND METHODS The seen
patients
in the present
study were Hospital
at either the Children's
Medical Center or the Cincinnati General Hospital, Cincinnati. Posterior nasopharyngeal cultures were taken with cotton-tipped wire swabs and inoculated onto Bordet Gengou medium. The medium was prepared each week and contained 20% sheep blood and 0.2 units of penicillin per ml. The cultures were incubated at 37 C and examined for one week. Colonies with the characteristics of Bordetella organisms were Gram stained, and then tested by slide agglutination and fluorescent anti¬ body staining with specific antisera.
RESULTS
Epidemiology Between April and December of 1974, a total of 37 cases of Bordetella infections were diagnosed in Cincin¬ nati, excluding those involved in a hospital-associated epidemic, which has been described." Twenty-nine of these patients had pertussis infec¬ tions. In addition to patients, a nasopharyngeal culture positive for pertussis was taken from a sibling of a patient, although this individual was asymptomatic at the time the culture was obtained. This child was not subsequently followed up to deter-
. PARAPERTUSSIS
m k
ML
. PERTUSSIS
7 21
5
Apr
May
19
, ,
2 16 30 14 28 II 25 8 22 6 20 3 17 Jun Jul Nov Aug Sep Oct
15 Dec
DATE OF POSITIVE CULTURE
Fig 1—Cases of Bordetella pertussis and Bordetella paraper¬ tussis diagnosed in Cincinnati, April through December 1974, by
Fig 2.—Chest roentgenogram from child with Bordetella paraper¬ tussis and pneumonia (patient 2).
date of positive culture.
Demonstrated Bordetella parapertussis Infections in Cincinnati, 1974 WBC Count (per
Patient/Age,
wk/Sex
1/6/M 2/7/F 3/19/F 4/20/M
5/20/M 6/25/F 7/27/M 8/30/F
Symptoms" C,V,W C,V C,V C
C,V c.v.w c
mm)
Lymphocytes,
Total
% 85 69 49 82 84
16,500 46,600 8,100 17,600 14,300
C
cu
Treatmentf
fNot done
8,700 11,500
H,E H,E None E
,E E
60
,E
56
None
Family
Cultures Not done
pertussis
Not done
pertussis
Negative
Not done Not done Not done
!,C indicates paroxysmal cough; V, vomiting; W, whooping cough. tH indicates hospitalization; E, erythromycin.
mine if he developed symptoms and did not return to the hospital for treatment. Eight patients (22%) had parapertussis grown from cultures taken from the nasopharynx. per¬ tussis was isolated at least once a month from April through December, yielding from zero to three positive cultures a week (Fig 1). The largest cluster of cases occurred in August. Bordetella parapertussis isolation showed a similar distribution, but four of the eight isolations were made in July. Positive cultures were obtained in June, July, August, October, and November. Clinical Illness
The eight patients with paraper¬ tussis included four boys and four girls (Table). The ages ranged from 6 to 30 weeks, with a mean of 19 weeks. Only one of the children had received a series of three immunizations for pertussis. All of them had paroxysmal coughing. None had temperatures over 38 C Symptoms had begun one to
two weeks before the patient was seen, except for patients 7 and 8, who had a history of onset four to six
weeks
prior. Five of the patients had vomiting after coughing, and two patients had an inspiratory whoop (patients 1 and 7). All of the patients improved within two weeks after they were seen, except for patient 2, who is
described in detail later. One child had an exacerbation of paroxysmal cough¬
ing and vomiting cent stage.
during the convales¬
Four of the seven children who had WBC counts taken had lymphocytosis (Table), and one child had a total WBC count of 46,600/cu mm. All five chil¬ dren had chest roentgenograms that were normal. The chest roentgeno¬ gram of patient 2 was abnormal later in her illness. Bordetella paraper¬ tussis was isolated from cultures taken from the posterior nasopharynx of all eight patients. In five patients, the isolate was initially reported as pertussis, but subsequently identified as
parapertussis.
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The illness in two of the patients mild that no treatment was given (Table). One of these patients was examined again one week after the positive culture and was asympto¬ matic. Two other patients were given erythromycin and sent home. Four patients were admitted to the hospital and three of these were hospitalized for 3, 5, and 11 days, respectively. The fourth patient died. Family histories, obtained in six of the cases, revealed four families in which other family members had symptoms of respiratory tract infec¬ tions. The mother and a sibling of each of three infants had paroxysmal coughing, as did the uncle of a fourth infant. The families of three of these patients (2, 4, 5) had nasopharyngeal cultures. Bordetella parapertussis was not recovered from any of the was so
family members; however, pertussis serotype 1,3,6 was recovered from the mother and sister of patient 2, and from the mother of patient 4 (Table). REPORT OF A CASE A 7-week-old female infant
(patient 2)
admitted to the Children's Hospital Medical Center on October 25, 1974, for severe paroxysmal coughing. The child had been delivered at 33 weeks' gestation, weighing 1,813 gm. After discharge, she was in good health until two weeks prior to admission, when she developed an upper respiratory tract infection with rhinorrhea followed by sneezing and coughing. During the week before admission, her cough became progressively worse until she was having paroxysms every 10 to 15 minutes, lasting a minute. She was in moderate was
distress during the paroxysms, which were followed by vomiting. At the time of admission she was afebrile. Position
change, pain, paroxysms of
or feeding precipitated coughing that produced
white, frothy sputum, The WBC count was
46,600/cu mm with 69% lymphocytes, 9% monocytes, 2% eosinophiles, and 20% poly¬
morphonuclear leukocytes. roentgenograms showed
coarse
The
chest
lung mark¬
ings extending from both hila, and para¬ pertussis grew from a nasopharyngeal culture. The infant was given intravenous fluid and oral erythromycin. She remained afebrile, but the paroxysms of coughing continued, with little sputum production. Four days after admission she became more tachypneic and cyanotic, with perior¬ bital and ankle edema. A repeat chest roentgenogram showed a "shaggy" heart border with infiltrates in both upper lobes and the right lower lobe (Fig 2). During a lumbar puncture, she had a respiratory arrest and was intubated and placed in an oxygen hood. Examination of her chest at this time revealed inspiratory wheezes and rhonchi. Therapy with ampicillin sodium and gentamicin sulfate was initiated, and blood cultures taken prior to these antibiot¬ ics were subsequently sterile. The follow¬ ing day she began having seizures, and the fontanelle was noted to be bulging. Treat¬ ment included phénobarbital, diazepam, dexamethasone and mannitol, and she was given mechanical respiratory assistance. On the seventh hospital day, a two-volume exchange transfusion was given. She developed bradycardia, became hypotensive, and died. Autopsy revealed a bronchiolitis with bronchopneumonia involving all lobes, with areas of focal necrosis, hemorrhagic ede¬ ma, and hyaline membranes. Routine post¬ mortem cultures of the lungs and blood were sterile. Cerebral edema was present with widespread anoxic changes including severe neuronal necrosis. The liver, on gross dissection, showed focal yellow areas with mild fatty changes limited to periportal areas on microscopical sections. Superficial erosions of the larynx, trachea and stomach were present. There was lymphoid depletion of the spleen, intestinal tract, and lymph nodes, with accelerated involution of the thymus. Both the mother and an 8-year-old sibling had paroxysmal coughs at the time of the patient's illness. Bordetella pertussis serotype 1,3,6 grew from nasopharyngeal cultures of both of them.
REVIEW OF THE LITERATURE
Thirty years after Bordet and Gengou first isolated pertussis,10 Elder-
ing and Kendrick1 noted that some of their isolates grew usually large on cough plates with continued incuba¬ tion and could be grown on plain infu¬ sion agar in contrast to typical pertussis. Bradford and Slavin- also noted atypical organisms that pro¬ duced a definite zone of hemolysis after 24 hours incubation, whereas typical pertussis required 72 hours to produce hemolysis. The studies of these two groups demonstrated that the atypical organism differed from both pertussis and bronchiseptica, and Eldering and Kendrick suggested the name parapertussis. Clinical studies have also shown that the two infections are distinct, since children who develop one infection remain susceptible to infection from the other organism." The frequency with which para¬ pertussis occurs is difficult to deter¬ mine because of the limited number of studies searching specifically for this organism. Two types of studies exist: (1) the results of cultures taken from children with clinical pertussis; and (2) serologie surveys for antibodies to parapertussis. In the United States, the most extensive experience in obtaining cultures from children with pertussis has come from the labora¬ tory of Eldering and Kendrick.1 Over a 16-year period, from 1935 to 1950, they found parapertussis in 106 of 4,483 (2.4%) cultures positive for Bordetella organisms. The cultures were obtained from 3,328 patients, including 65 patients with paraper¬ tussis. In Denmark, Lautrop reported finding parapertussis in 1,801 of 43,185 (4.2%) Bordetella isolates recov¬ ered between 1946 and 1970.' During studies on the efficacy of pertussis vaccine in the United Kingdom, parapertussis was isolated in six of 1,084 (0.6%) positive Bordetella cul¬ tures." Experience over four years in Bulgaria, after mass immunizations with pertussis vaccine, indicated that parapertussis was responsible for 17.4% of cases with paroxysmal coughs.5 In Moscow, 276 of 930 (30%) children with clinical pertussis during a three-month period had paraper¬ tussis.''' One problem with these stud¬ ies is that they reflect only the cases of severe pertussis syndrome caused
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by parapertussis. Serologie surveys provide a better indication of the frequency of infections. In 1941,
Miller et al" tested 50 children in California and found that 20 (40%) had antibody to parapertussis. Flosdorf et al'4 measured antibody in several populations and demonstrated that 91% of urban adults had antibody. Serologie studies in Europe have also shown antibodies in more than 50% of adults." These studies indicate the parapertussis infections are extreme¬
ly widespread, although they are not recognized clinically. The only bactéri¬ ologie survey of a general population to determine the prevalence of parapertussis was done in Czechoslo¬
vakia.7 Cultures were obtained from a total of 9,983 children over a two-year period, and 173 (1.73%) had positive cultures. No similar studies have been reported in the United States. The European studies have also provided the best description of the clinical spectrum of parapertussis infections.7'" Clinically recognized in¬ fections occur primarily in children less than 10 years of age. Less than 20% of infected children have present¬ ing symptons of clinical pertussis, and
approximately 40% are asymptomatic.
This is in contrast to those with in whom asymptomatic infections are extremely rare.17 The remaining patients have mild coughs, which would be diagnosed clinically as bronchitis. In most cases, the illness lasts less than three weeks. However, half of the patients continue to excrete the organism for more than five weeks. Although most of the patients had mild disease, occasionally severe disease with leukocytosis and lymphocytosis have been reported.-·'" In 1946, Zuelzer and Wheeler8 re¬ ported two fatal cases, two children with parapertussis pneumonia.
pertussis,
COMMENT the In present study, 22% of the with demonstrated Borde¬ patients tella infections had parapertussis. This percentage seemed unusually high compared to other reported studies in which less than 5% of isolates from patients with pertussis were parapertussis. However, these percentages are based on the long-
term studies cited above.'·4 In
studies
Europe,
short periods of time coinciding with epidemics of para¬ pertussis have shown this organism in as many as 30% of patients." There¬ fore, one possible explanation for the increase in parapertussis in Cincin¬ nati was the occurrence of an epidemic during the study period. The distribution of cases does not specifi¬ cally indicate an epidemic (Fig 1), but it is possible that an epidemic was occurring throughout the year and only the more severe cases were detected. Bordetella parapertussis probably occurs more commonly in this country than is generally recog¬ nized. The high percentage of cases in this study may reflect the fact that cultures were obtained from children with relatively mild disease, and all isolates were serotyped. To define the prevalence of disease in the United States, bactériologie surveys of large populations are needed, similar to that reported in Czechoslovakia.7 Although parapertussis does not usually cause severe disease as does pertus¬ sis, it may be a major cause of prolonged bronchitis. Clinically, most over
of these cases would be attributed to viral infections. This study also raises the question of how severe a disease may be, caused by parapertussis. Four of the eight patients required hospital¬ ization and one of them died. How¬ ever, all of the patients were very young children. It is possible that many mild infections were occurring in older children and adults and were not diagnosed. Surprisingly, in two of three families from whom cultures were obtained, pertussis was iso¬ lated at the same time that the patient had parapertussis, includ¬ ing the patient who died of pneumo¬ nia. Also, four of the patients had
lymphocytosis. Although lymphocyto¬ sis has been reported in patients with parapertussis, this rate of oc¬ currence is unusual especially since it has been stated that this organism does not produce a lymphocytosispromoting factor.1'1 These observa¬ tions suggest that the
parapertussis
may
severe cases
of
represent dual
infections with pertussis. In the original article by Eldering and Ken¬ drick,1 the most severe case of pertus-
sis in their seven patients had a culture positive for both organisms. Other cases of dual infections with pertussis and parapertussis have been mentioned, and simultaneous epidemics caused by the two organ¬ isms in closed populations have been reported.5·"·11·15·'" The difficulty in ap¬ preciating the presence of both orga¬ nisms is not surprising. Bordetella
parapertussis was initially misdiagnosed as pertussis in five of eight cases in this study. To detect both organisms in a culture would require examining several colonies on each plate, and perhaps using selective media.
Dr Kevin Bove reviewed the autopsy findings in patient 2. The case of patient 2 is reported with the permission of Dr R. Youngpeters, the patient's physician. All isolates were serotyped by Jack Holwerda, Michigan Department of Public Health.
Nonproprietary Names and Trademarks of Drugs Ampicillin s,od\xim-Alpen-N, Amcill-S, Omnipen-N, Penbritin-S, Polycillin-N, Principen IN. Gentamicin sulfate—Garamycin.
References 1. Eldering G, Kendrick P: Bacillus parapertussis: A species resembling both bacillus pertussis and bacillus bronchisepticus but identical with neither. J Bacteriol 35:561-572, 1938. 2. Bradford WL, Salvin B: An organism resembling Hemophilus pertussis with special reference to color changes produced by its growth
upon certain media. Am J Public Health 27:1277\x=req-\ 1282, 1937. 3. Eldering G, Kendrick PL: Incidence of parapertussis in the Grand Rapids area as indicated by 16 years' experience with diagnostic cultures. Am J Public Health 42:27-31, 1952. 4. Lautrop H: Epidemics of parapertussis: Twenty years' observations in Denmark. Lancet 1:1195-1198, 1971. 5. Donchev D, Stoyanova M: The epidemiological significance of the differentiation of pertussis and parapertussis. J Hyg Epidemiol Microbiol Immunol 5:294-297, 1961. 6. Neimark FM, Lugovaya LV, Belova ND: Bordetella parapertussis and its significance in the incidence of pertussis. Zh Mikrobiol Epidemiol Immunobiol 32:49-53, 1961.
7. Borska K, Simkovicova M: Studies on the circulation of Bordetella pertussis and Bordetella parapertussis in populations of children. J Hyg Epidemiol Microbiol Immunol 16:159-172, 1972. 8. Zuelzer WW, Wheeler WE: Parapertussis pneumonia: Report of two fatal cases. J Pediatr 29:493-497, 1946. 9. Linnemann CC Jr, Ramundo N, Perlstein PH, et al: Use of pertussis vaccine in an epidemic involving hospital staff. Lancet 2:540-543, 1975. 10. Bordet J, Gengou O: La microbe de la Coqueluche. Ann Inst Pasteur 20:731, 1906. 11. Lautrop H: Observations on parapertussis in Denmark, 1950-1957. Acta Pathol Microbiol Scand 43:255-266, 1958. 12. Public Health Laboratory Service: Efficacy of whooping-cough vaccines used in the United Kingdom before 1968. Br Med J 1:259-262, 1973. 13. Miller JJ Jr, Saito TM, Silverberg RJ: Parapertussis: Clinical and serologic observations. J Pediatr 19:229-240, 1941. 14. Flosdorf EW, Bondi A, Felton H, et al: Studies with Hemophilus pertussis: X. Comparative antigenic analysis of Bacillus parapertussis
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and Hemophilus pertussis. Phase I, with consideration of clinical significance. J Pediatr 21:625\x=req-\ 634, 1942. 15. Vysoka-Burianova B: Contemporary problems in the epidemiology of whooping cough. J Hyg Epidemiol Microbiol Immunol 7:472-481, 1963. 16. Vysoka B: The epidemiology of pertussis and parapertussis. J Hyg Epidemiol Microbiol Immunol 2:196-204, 1958. 17. Linnemann CC, Bass JW, Smith MHD: The carrier state in pertussis. Am J Epidemiol 88:422\x=req-\ 427, 1968. 18. Morse JH, Morse SI: Studies on the ultrastructure of Bordetella pertussis: I. Morphology, origin, and biological activity of structures present in the extracellular fluid of liquid cultures of Bordetella pertussis. J Exp Med 131:1342-1357, 1970. 19. Laboratory diagnosis and prevention of whooping-cough. Summary of proceedings, 117th annual meeting of the British Medical Association. Br Med J 2:72-73, 1949.
Experience
parapertussis
and
Calvin C. Linnemann, Jr, MD,
a
Evelyn
Review of the Literature B.
Perry
\s=b\ During 1974, eight of 37 (22%) Bordetella organisms isolated from patients in Cincinnati were Bordetella parapertussis. This is in contrast to other experience in the United States where parapertussis has comprised < 5% of the Bordetella species isolated and suggests that B parapertussis infection may be more common in this country than generally recognized. The failure to appreciate the presence of this infection may result from the lack of cultures taken from children with mild disease and the failure to distinguish B
the
of Bordetella species dis¬ and capable of tinct from producing human disease, clinical ex¬ perience has suggested that this organism is a rare cause of mild pertussis.1·- In the United States and parapertussis has been Europe, reported as a cause of 5% or less of documented Bordetella infections.3-4 However, some European studies have suggested that this organism causes 20% to 30% of cases of pertussis syndrome, and may be more prevalent than pertussis.'-7 Although most reported cases of parapertussis
recognition Sinceparapertussis pertussis as
a
From the Infectious Disease Division, University of Cincinnati College of Medicine, and the Children's Hospital Medical Center, Cincinnati. Reprint requests to Infectious Disease Division, University of Cincinnati College of Medicine, 231 Bethesda Ave, Cincinnati, Ohio 45267
(Dr Linnemann).
parapertussis from
B pertussis. Cultures obtained from family members of three of the children with B parapertussis, and B pertussis was isolated from members of two families, including the mother and sister of a child who died of pneumonia and encephalopathy. These cases suggest that patients with severe disease associated with B parapertussis should be carefully evaluated for the possibility of dual infection caused by B pertussis. (Am J Dis Child 131:560-563, 1977) were
have been
mild, two cases of fatal pneumonia have been reported, which raises the question of whether the organism may cause severe disease.8
There are several reasons for the differences among the various stud¬ ies. Some of the studies represent experience over many years, whereas others report short-term surveys. True differences in prevalence among countries, failure to obtain cultures from patients with mild pertussis, and failure to distinguish the two orga¬ nisms may also account for some of these discrepancies. In the spring of 1974, an epidemic of
pertussis involving hospital personnel
occurred in Cincinnati." Because of this epidemic, pediatricians were alerted to culture all patients with paroxysmal coughs for pertussis. Dur¬ ing that year, 22% of Bordetella organisms isolated were paraper-
Downloaded From: http://archpedi.jamanetwork.com/ by a Oakland University User on 06/06/2015
tussis, including one from an infant who died of pneumonia and encepha¬ lopathy. This study reports the epi¬ demiologica! and clinical features of the patients with parapertussis. MATERIALS AND METHODS The seen
patients
in the present
study were Hospital
at either the Children's
Medical Center or the Cincinnati General Hospital, Cincinnati. Posterior nasopharyngeal cultures were taken with cotton-tipped wire swabs and inoculated onto Bordet Gengou medium. The medium was prepared each week and contained 20% sheep blood and 0.2 units of penicillin per ml. The cultures were incubated at 37 C and examined for one week. Colonies with the characteristics of Bordetella organisms were Gram stained, and then tested by slide agglutination and fluorescent anti¬ body staining with specific antisera.
RESULTS
Epidemiology Between April and December of 1974, a total of 37 cases of Bordetella infections were diagnosed in Cincin¬ nati, excluding those involved in a hospital-associated epidemic, which has been described." Twenty-nine of these patients had pertussis infec¬ tions. In addition to patients, a nasopharyngeal culture positive for pertussis was taken from a sibling of a patient, although this individual was asymptomatic at the time the culture was obtained. This child was not subsequently followed up to deter-
. PARAPERTUSSIS
m k
ML
. PERTUSSIS
7 21
5
Apr
May
19
, ,
2 16 30 14 28 II 25 8 22 6 20 3 17 Jun Jul Nov Aug Sep Oct
15 Dec
DATE OF POSITIVE CULTURE
Fig 1—Cases of Bordetella pertussis and Bordetella paraper¬ tussis diagnosed in Cincinnati, April through December 1974, by
Fig 2.—Chest roentgenogram from child with Bordetella paraper¬ tussis and pneumonia (patient 2).
date of positive culture.
Demonstrated Bordetella parapertussis Infections in Cincinnati, 1974 WBC Count (per
Patient/Age,
wk/Sex
1/6/M 2/7/F 3/19/F 4/20/M
5/20/M 6/25/F 7/27/M 8/30/F
Symptoms" C,V,W C,V C,V C
C,V c.v.w c
mm)
Lymphocytes,
Total
% 85 69 49 82 84
16,500 46,600 8,100 17,600 14,300
C
cu
Treatmentf
fNot done
8,700 11,500
H,E H,E None E
,E E
60
,E
56
None
Family
Cultures Not done
pertussis
Not done
pertussis
Negative
Not done Not done Not done
!,C indicates paroxysmal cough; V, vomiting; W, whooping cough. tH indicates hospitalization; E, erythromycin.
mine if he developed symptoms and did not return to the hospital for treatment. Eight patients (22%) had parapertussis grown from cultures taken from the nasopharynx. per¬ tussis was isolated at least once a month from April through December, yielding from zero to three positive cultures a week (Fig 1). The largest cluster of cases occurred in August. Bordetella parapertussis isolation showed a similar distribution, but four of the eight isolations were made in July. Positive cultures were obtained in June, July, August, October, and November. Clinical Illness
The eight patients with paraper¬ tussis included four boys and four girls (Table). The ages ranged from 6 to 30 weeks, with a mean of 19 weeks. Only one of the children had received a series of three immunizations for pertussis. All of them had paroxysmal coughing. None had temperatures over 38 C Symptoms had begun one to
two weeks before the patient was seen, except for patients 7 and 8, who had a history of onset four to six
weeks
prior. Five of the patients had vomiting after coughing, and two patients had an inspiratory whoop (patients 1 and 7). All of the patients improved within two weeks after they were seen, except for patient 2, who is
described in detail later. One child had an exacerbation of paroxysmal cough¬
ing and vomiting cent stage.
during the convales¬
Four of the seven children who had WBC counts taken had lymphocytosis (Table), and one child had a total WBC count of 46,600/cu mm. All five chil¬ dren had chest roentgenograms that were normal. The chest roentgeno¬ gram of patient 2 was abnormal later in her illness. Bordetella paraper¬ tussis was isolated from cultures taken from the posterior nasopharynx of all eight patients. In five patients, the isolate was initially reported as pertussis, but subsequently identified as
parapertussis.
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The illness in two of the patients mild that no treatment was given (Table). One of these patients was examined again one week after the positive culture and was asympto¬ matic. Two other patients were given erythromycin and sent home. Four patients were admitted to the hospital and three of these were hospitalized for 3, 5, and 11 days, respectively. The fourth patient died. Family histories, obtained in six of the cases, revealed four families in which other family members had symptoms of respiratory tract infec¬ tions. The mother and a sibling of each of three infants had paroxysmal coughing, as did the uncle of a fourth infant. The families of three of these patients (2, 4, 5) had nasopharyngeal cultures. Bordetella parapertussis was not recovered from any of the was so
family members; however, pertussis serotype 1,3,6 was recovered from the mother and sister of patient 2, and from the mother of patient 4 (Table). REPORT OF A CASE A 7-week-old female infant
(patient 2)
admitted to the Children's Hospital Medical Center on October 25, 1974, for severe paroxysmal coughing. The child had been delivered at 33 weeks' gestation, weighing 1,813 gm. After discharge, she was in good health until two weeks prior to admission, when she developed an upper respiratory tract infection with rhinorrhea followed by sneezing and coughing. During the week before admission, her cough became progressively worse until she was having paroxysms every 10 to 15 minutes, lasting a minute. She was in moderate was
distress during the paroxysms, which were followed by vomiting. At the time of admission she was afebrile. Position
change, pain, paroxysms of
or feeding precipitated coughing that produced
white, frothy sputum, The WBC count was
46,600/cu mm with 69% lymphocytes, 9% monocytes, 2% eosinophiles, and 20% poly¬
morphonuclear leukocytes. roentgenograms showed
coarse
The
chest
lung mark¬
ings extending from both hila, and para¬ pertussis grew from a nasopharyngeal culture. The infant was given intravenous fluid and oral erythromycin. She remained afebrile, but the paroxysms of coughing continued, with little sputum production. Four days after admission she became more tachypneic and cyanotic, with perior¬ bital and ankle edema. A repeat chest roentgenogram showed a "shaggy" heart border with infiltrates in both upper lobes and the right lower lobe (Fig 2). During a lumbar puncture, she had a respiratory arrest and was intubated and placed in an oxygen hood. Examination of her chest at this time revealed inspiratory wheezes and rhonchi. Therapy with ampicillin sodium and gentamicin sulfate was initiated, and blood cultures taken prior to these antibiot¬ ics were subsequently sterile. The follow¬ ing day she began having seizures, and the fontanelle was noted to be bulging. Treat¬ ment included phénobarbital, diazepam, dexamethasone and mannitol, and she was given mechanical respiratory assistance. On the seventh hospital day, a two-volume exchange transfusion was given. She developed bradycardia, became hypotensive, and died. Autopsy revealed a bronchiolitis with bronchopneumonia involving all lobes, with areas of focal necrosis, hemorrhagic ede¬ ma, and hyaline membranes. Routine post¬ mortem cultures of the lungs and blood were sterile. Cerebral edema was present with widespread anoxic changes including severe neuronal necrosis. The liver, on gross dissection, showed focal yellow areas with mild fatty changes limited to periportal areas on microscopical sections. Superficial erosions of the larynx, trachea and stomach were present. There was lymphoid depletion of the spleen, intestinal tract, and lymph nodes, with accelerated involution of the thymus. Both the mother and an 8-year-old sibling had paroxysmal coughs at the time of the patient's illness. Bordetella pertussis serotype 1,3,6 grew from nasopharyngeal cultures of both of them.
REVIEW OF THE LITERATURE
Thirty years after Bordet and Gengou first isolated pertussis,10 Elder-
ing and Kendrick1 noted that some of their isolates grew usually large on cough plates with continued incuba¬ tion and could be grown on plain infu¬ sion agar in contrast to typical pertussis. Bradford and Slavin- also noted atypical organisms that pro¬ duced a definite zone of hemolysis after 24 hours incubation, whereas typical pertussis required 72 hours to produce hemolysis. The studies of these two groups demonstrated that the atypical organism differed from both pertussis and bronchiseptica, and Eldering and Kendrick suggested the name parapertussis. Clinical studies have also shown that the two infections are distinct, since children who develop one infection remain susceptible to infection from the other organism." The frequency with which para¬ pertussis occurs is difficult to deter¬ mine because of the limited number of studies searching specifically for this organism. Two types of studies exist: (1) the results of cultures taken from children with clinical pertussis; and (2) serologie surveys for antibodies to parapertussis. In the United States, the most extensive experience in obtaining cultures from children with pertussis has come from the labora¬ tory of Eldering and Kendrick.1 Over a 16-year period, from 1935 to 1950, they found parapertussis in 106 of 4,483 (2.4%) cultures positive for Bordetella organisms. The cultures were obtained from 3,328 patients, including 65 patients with paraper¬ tussis. In Denmark, Lautrop reported finding parapertussis in 1,801 of 43,185 (4.2%) Bordetella isolates recov¬ ered between 1946 and 1970.' During studies on the efficacy of pertussis vaccine in the United Kingdom, parapertussis was isolated in six of 1,084 (0.6%) positive Bordetella cul¬ tures." Experience over four years in Bulgaria, after mass immunizations with pertussis vaccine, indicated that parapertussis was responsible for 17.4% of cases with paroxysmal coughs.5 In Moscow, 276 of 930 (30%) children with clinical pertussis during a three-month period had paraper¬ tussis.''' One problem with these stud¬ ies is that they reflect only the cases of severe pertussis syndrome caused
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by parapertussis. Serologie surveys provide a better indication of the frequency of infections. In 1941,
Miller et al" tested 50 children in California and found that 20 (40%) had antibody to parapertussis. Flosdorf et al'4 measured antibody in several populations and demonstrated that 91% of urban adults had antibody. Serologie studies in Europe have also shown antibodies in more than 50% of adults." These studies indicate the parapertussis infections are extreme¬
ly widespread, although they are not recognized clinically. The only bactéri¬ ologie survey of a general population to determine the prevalence of parapertussis was done in Czechoslo¬
vakia.7 Cultures were obtained from a total of 9,983 children over a two-year period, and 173 (1.73%) had positive cultures. No similar studies have been reported in the United States. The European studies have also provided the best description of the clinical spectrum of parapertussis infections.7'" Clinically recognized in¬ fections occur primarily in children less than 10 years of age. Less than 20% of infected children have present¬ ing symptons of clinical pertussis, and
approximately 40% are asymptomatic.
This is in contrast to those with in whom asymptomatic infections are extremely rare.17 The remaining patients have mild coughs, which would be diagnosed clinically as bronchitis. In most cases, the illness lasts less than three weeks. However, half of the patients continue to excrete the organism for more than five weeks. Although most of the patients had mild disease, occasionally severe disease with leukocytosis and lymphocytosis have been reported.-·'" In 1946, Zuelzer and Wheeler8 re¬ ported two fatal cases, two children with parapertussis pneumonia.
pertussis,
COMMENT the In present study, 22% of the with demonstrated Borde¬ patients tella infections had parapertussis. This percentage seemed unusually high compared to other reported studies in which less than 5% of isolates from patients with pertussis were parapertussis. However, these percentages are based on the long-
term studies cited above.'·4 In
studies
Europe,
short periods of time coinciding with epidemics of para¬ pertussis have shown this organism in as many as 30% of patients." There¬ fore, one possible explanation for the increase in parapertussis in Cincin¬ nati was the occurrence of an epidemic during the study period. The distribution of cases does not specifi¬ cally indicate an epidemic (Fig 1), but it is possible that an epidemic was occurring throughout the year and only the more severe cases were detected. Bordetella parapertussis probably occurs more commonly in this country than is generally recog¬ nized. The high percentage of cases in this study may reflect the fact that cultures were obtained from children with relatively mild disease, and all isolates were serotyped. To define the prevalence of disease in the United States, bactériologie surveys of large populations are needed, similar to that reported in Czechoslovakia.7 Although parapertussis does not usually cause severe disease as does pertus¬ sis, it may be a major cause of prolonged bronchitis. Clinically, most over
of these cases would be attributed to viral infections. This study also raises the question of how severe a disease may be, caused by parapertussis. Four of the eight patients required hospital¬ ization and one of them died. How¬ ever, all of the patients were very young children. It is possible that many mild infections were occurring in older children and adults and were not diagnosed. Surprisingly, in two of three families from whom cultures were obtained, pertussis was iso¬ lated at the same time that the patient had parapertussis, includ¬ ing the patient who died of pneumo¬ nia. Also, four of the patients had
lymphocytosis. Although lymphocyto¬ sis has been reported in patients with parapertussis, this rate of oc¬ currence is unusual especially since it has been stated that this organism does not produce a lymphocytosispromoting factor.1'1 These observa¬ tions suggest that the
parapertussis
may
severe cases
of
represent dual
infections with pertussis. In the original article by Eldering and Ken¬ drick,1 the most severe case of pertus-
sis in their seven patients had a culture positive for both organisms. Other cases of dual infections with pertussis and parapertussis have been mentioned, and simultaneous epidemics caused by the two organ¬ isms in closed populations have been reported.5·"·11·15·'" The difficulty in ap¬ preciating the presence of both orga¬ nisms is not surprising. Bordetella
parapertussis was initially misdiagnosed as pertussis in five of eight cases in this study. To detect both organisms in a culture would require examining several colonies on each plate, and perhaps using selective media.
Dr Kevin Bove reviewed the autopsy findings in patient 2. The case of patient 2 is reported with the permission of Dr R. Youngpeters, the patient's physician. All isolates were serotyped by Jack Holwerda, Michigan Department of Public Health.
Nonproprietary Names and Trademarks of Drugs Ampicillin s,od\xim-Alpen-N, Amcill-S, Omnipen-N, Penbritin-S, Polycillin-N, Principen IN. Gentamicin sulfate—Garamycin.
References 1. Eldering G, Kendrick P: Bacillus parapertussis: A species resembling both bacillus pertussis and bacillus bronchisepticus but identical with neither. J Bacteriol 35:561-572, 1938. 2. Bradford WL, Salvin B: An organism resembling Hemophilus pertussis with special reference to color changes produced by its growth
upon certain media. Am J Public Health 27:1277\x=req-\ 1282, 1937. 3. Eldering G, Kendrick PL: Incidence of parapertussis in the Grand Rapids area as indicated by 16 years' experience with diagnostic cultures. Am J Public Health 42:27-31, 1952. 4. Lautrop H: Epidemics of parapertussis: Twenty years' observations in Denmark. Lancet 1:1195-1198, 1971. 5. Donchev D, Stoyanova M: The epidemiological significance of the differentiation of pertussis and parapertussis. J Hyg Epidemiol Microbiol Immunol 5:294-297, 1961. 6. Neimark FM, Lugovaya LV, Belova ND: Bordetella parapertussis and its significance in the incidence of pertussis. Zh Mikrobiol Epidemiol Immunobiol 32:49-53, 1961.
7. Borska K, Simkovicova M: Studies on the circulation of Bordetella pertussis and Bordetella parapertussis in populations of children. J Hyg Epidemiol Microbiol Immunol 16:159-172, 1972. 8. Zuelzer WW, Wheeler WE: Parapertussis pneumonia: Report of two fatal cases. J Pediatr 29:493-497, 1946. 9. Linnemann CC Jr, Ramundo N, Perlstein PH, et al: Use of pertussis vaccine in an epidemic involving hospital staff. Lancet 2:540-543, 1975. 10. Bordet J, Gengou O: La microbe de la Coqueluche. Ann Inst Pasteur 20:731, 1906. 11. Lautrop H: Observations on parapertussis in Denmark, 1950-1957. Acta Pathol Microbiol Scand 43:255-266, 1958. 12. Public Health Laboratory Service: Efficacy of whooping-cough vaccines used in the United Kingdom before 1968. Br Med J 1:259-262, 1973. 13. Miller JJ Jr, Saito TM, Silverberg RJ: Parapertussis: Clinical and serologic observations. J Pediatr 19:229-240, 1941. 14. Flosdorf EW, Bondi A, Felton H, et al: Studies with Hemophilus pertussis: X. Comparative antigenic analysis of Bacillus parapertussis
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and Hemophilus pertussis. Phase I, with consideration of clinical significance. J Pediatr 21:625\x=req-\ 634, 1942. 15. Vysoka-Burianova B: Contemporary problems in the epidemiology of whooping cough. J Hyg Epidemiol Microbiol Immunol 7:472-481, 1963. 16. Vysoka B: The epidemiology of pertussis and parapertussis. J Hyg Epidemiol Microbiol Immunol 2:196-204, 1958. 17. Linnemann CC, Bass JW, Smith MHD: The carrier state in pertussis. Am J Epidemiol 88:422\x=req-\ 427, 1968. 18. Morse JH, Morse SI: Studies on the ultrastructure of Bordetella pertussis: I. Morphology, origin, and biological activity of structures present in the extracellular fluid of liquid cultures of Bordetella pertussis. J Exp Med 131:1342-1357, 1970. 19. Laboratory diagnosis and prevention of whooping-cough. Summary of proceedings, 117th annual meeting of the British Medical Association. Br Med J 2:72-73, 1949.
