B A C I L L U S E N T E R I T I D I S M E N I N G I T I S IN AN I N F A N T OF FIFTEEN MONTHS JOHN O. VAUGH~, M.D. SANTA ~VIoNICA, CALIF.
Shelburne 1 reviewed tile cases of meningitis caused I Nby]930bacilliL y nofc h theand paratyphoid group. Despite the nmnerous reports on record, they accepted only fifteen cases in which identification of the organisms was based on indisputable cultural or serologic evidence. They added a sixteenth case due to the Bacillus enteritidis of Giirtner and concluded that meningitis due to bacilli of this group is a serious condition, usually fatal, and should be suspected whenever gram-negative motile rods are found in the eerebrospinal fluid. Cooke and Bell 2 emphasized the fact that meningeal infection by organisms of this group is sharply limited to early infancy. The majority of the patients noted ,by other observers are under one year of age. As an explanation of the age incidence, they suggest three factors: (1) the greater permeability of the intestinal mucosa in early infancy; (2) decreased resistance of young infants to bacterial infection associated with defective antibody formation; and (3) the influence of digestive disturbances and malnutrition on the above mentioned factors. In a recent review of 705 eases of meningitis occurring in children, Fothergill and Sweet :~ stated that organisms of the colon group caused nine of the cases. Eight of these patients were under five weeks of age. A bacteremia was almost universally present. In the majority of eases there was a relatively high percentage of mononuclear cells in the spinal fluid compared to other types of purulent meningitis. The variable symptomatology of infection with Bacillus enteritidis in older individuals is well illustrated in the case reported by Me Nee. ~ IIis twenty-five-year-old male patient presented the picture of influenza complicated with pneumonia and acute hemorrhagic nephritis. No diarrheal symptoms occurred. The pus expressed from the bronchi at autopsy revealed an almost pure culture of Bacillus enteritidis as did a culture from the spleen. Cerebral edema was present but there was no evidence of purulent meningitis. One h u n d r e d consecutive cases of meningitis observed from 1927 to 1931 at the Los Angeles Children's Hospital were reviewed and classified as shown in Table I. From the Los Ang'eles Children's Hospital. 631
632
THE JOURNAL OF PEDIATt%ICS TABLE I DIST[~IBUTION T Y P E OF IVIENINGITIS
OF TYPES
OF I~[ENINGITIS AGE LIMITS
B. tuberculosis Nieningoccoccus Streptococcus (Alpha type) B. ~nfluenzae Streptococcus (Beta type) Pneumoeoccus Streptococcus (not typed) Streptococcus mueosus Staphylococcus (not typed) B. col~ vommueis B. e~te~itid~s Syphilitic
6 2 1 I 2 2 2 7 2 5 15 1
too.-9 yr. too.-7 yr. mo.-6 yr. yr.-4 yr. yr.-10 yr. mo.-2 yr. mo.-8 yr. yr. days too. too. yr.
N U M B E I % Ol~ O A S E S
59. 12 11 7 6 4 3 1 ] 1 1
1
I n Table I only those cases of tuberculous meningitis are included in which the organism was demonstrated in smears f r o m the spinal fluid or in which conclusive gross microscopic evidence was present at autopsy. I n the other nontuberculous eases the organisms were obtained f r o m spinal fluid cultures d u r i n g life with the exception of a few instances in which the culture was obtained f r o m the exudate at autopsy. The large number of tuberculosis eases was p a r t l y dependent on the large Mexican population in which the disease is p a r t i c u l a r l y prevalent. The relatively small n u m b e r of meningocoecus cases was due to the absence of this disease in epidemic form at the time these eases were observed. M o r t a l ity figures in the meningocoeeus eases are not available, because of the t r a n s f e r of these patients to the Contagious Division of the Los Angeles General Hospital as soon as the diagnosis was established. Mortality in the remainder of the series was universal, with the single exception of the one syphilitic case. The one ease in this series caused by BaciLlus enteritidis will be reported in detail. REPORT OF CASE IIisto~'y.--L. P., a white female, fifteen months old, entered the llospital on May 31, 1931. Birth and previous history were not unusual. Bc~th parents and an older brother were living and well. The patient had been well until two weeks before when a " h e a d c o l d " associated with several loose stools daily was noted. ~'ever, vomiting, and listlessness developed. Three days following the onset of illness, there occurred a general convulsion of one and one-half hours' duration. The child became progressively stuporous, and convulsive seizures were repeated on three occasions. Phys4cal g z a m i n a t i o n . - - T h e child was dehydrated and poorly nourished, weighing seventeen poun4s. She was stuporous and aroused with difficulty. Marked ne(,k rigidity was present; occasional purposeless fluttering movements of the hands and slight weakness of the left arm and leg, were noted. The pharynx was inflamed. No other abnormalities were observed. Laboratory D a t a . - - T h e spinal fluid was cloudy and under increased pressure. Cell counts on various occasions ranged from 500 to 6500 cells per cubic milli-
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BACILLUS ENTERIT1DIS MENINGITIS
meter, 98 per cent of which were p u s cells. Blood e x a m i n a t i o n showed 38 per cent h e m o g l o b i n ( D a r e ) a n d 2,660~000 erythrocytes. L e u c o c y t e s n u m b e r e d 2.1,900. A differential count showed: p o l y m o r p h o n u c l e a r s , 86 per cent; lymphocytes, 11 p e r c e n t ; m o n o n u c l e a r s , 3 p e r cent. U r i n e e x a m i n a t i o n w a s n e g a t i v e except for a f a i n t t r a c e o f a l b u m i n . S p i n a l fluid a n d blood cultures produced B. enteritidis ( G ~ r t n e r ) w h i c h w a s confirmed b y cultural a n d serologic study. Bacteriological Diagnosis.--Morphology a n d S t a i n i n g . Direct s m e a r s f r o m t h e p u r u l e n t c e r e b r o s p i n a l fluid s t a i n e d with G r a m ' s m e t h o d revealed n u m e r o u s cells, a n d g r a m - n e g a t i v e , n o n s p o r i f e r o u s ro4% m o s t l y extracellular. The differential c o u n t was 98 p e r cent p o l y m o r p h o n n c l e a r cells a n d 2 p e r cent lymphocytes. T h e bacilli proved to be actively motile w h e n some of t h e fluid was placed on a h a n g i n g drop slide. C u l t u r a l Characteristics. The o r g a n i s m s in the s p i n a l fluid grew a b u n d a n t l y in veal broth~ on blood a g a r plates, on bacto-eosin m e t h y l e n e blue a g a r plates, on b a c t e n u t r i e n t a g a r , a n d on h e a r t i n f u s i o n a g a r slants. T h e rods m e a s u r e d f r o m 1.69 to 1.81 m i c r o n s in l e n g t h a n d 0.338 m i c r o n i n width. T h e s e m e a s u r e m e n t s were t a k e n a f t e r t h e o r g a n i s m s h a d been t r a n s p l a n t e d several times. T h e s u r f a c e colonies m e a s u r e d f r o m 1 to 2 ram. in diameter. T h e colonies were finely g r a n u l a r in s t r u c t u r e a l t h o u g h t h e y h a d a s m o o t h a p p e a r a n c e . T h e edges of t h e colonies were t h i n while t h e centers were s o m e w h a t dome s h a p e d . There was no hemolysis producecI on blood a g a r plates. I n veal b r o t h a pe]licle w a s f o r m e d a f t e r seventytwo h o u r s of i n c u b a t i o n . On veal blood a g a r t h e g r o w t h w a s slightly g r a y in color; on eosin m e t h y l e n e blue a g a r plate% t h e colonies were f a i n t l y p i n k ; a n d on bacton u t r i e n t a g a r a n d h e a r t i n f u s i o n m e d i a the g r o w t h w a s yellow in color a n d b u t r y o u s in consistency. Cultures f r o m t h e spinal fluid o b t a i n e d a t t h e second a n d t h i r d lumbar punctures produced the same organisms. A blood culture t a k e n J u n e 6~ 1931~ p r o d u c e d o r g a n i s m s identical with t h o s e founcI i n t h e s p i n a l fluid a f t e r 48 h o u r s ' i n c u b a t i o n . Biochemical R e a c t i o n s . - - T h e o r g a n i s m s p r o d u c e d i n c u l t u r e f r o m the s p i n a l fluid a n d blood f o r m e d acid a n d g a s in a 1 per cent c a r b o h y d r a t e m e d i u m of dextrose, m a n n i t % a n d maltose. F e r m e n t a t i o n was n o t p r o d u c e d in lactose or ~n saccharose. I n d o l was n e g a t i v e . Serologic R e a e t i o n s . ~ - - T e c h n i c of A g g l u t i n a t i o n Tests. Typhold~ p a r a A . a n d p a r a B a n t i s e r u m s , a n d e n t e r i t i d i s a n t i s e r u m , were u s e d in t h e tests. TABLE II
[~ESULTS OF AGGLUTINATION TESTS WIT]=[ ORGANISM~ FRONI SPINAL FLUID. ORGANISlV[ I~ IN SPII~AL FLUID DILUTIONS Antiserum Typhoid Para A Para B Enteritldis
L20 + . + +
40 + . + +
80 +
160 . .
+ +
+ +
ANTIGEN
OF ANTISEI~UMS
320 640 1,280 . . . . . . . .
.
.
+
+
+
2,560 . .
5,].20
10,240
20,480
.
+
+
The antigen was made by washing with sterile normal saline nutrient agar slants of 24-hour cultures from the spinal fluid and blood of the patient. Three drop~ of I0 per cent formalin was added to the suspension to inhibit growth. One tenth of one cubic centimeter of each of the antiserums was used. After the agglutination t e s t s were prepared~ t h e y were s h a k e n well a n d i n c u b a t e d o v e r n i g h t a t 37.5 ~ F. T h e n e x t m o r n i n g t h e t e s t s were placed in t h e ice b o x f o r h a l f a n h o u r b e f o r e r e a d i n g . *The typhoid, p a r a A a n d p a r a B, a n t i s e r u m s u s e d in t h e tests were p u r c h a s e d f r o m Parke, D a v i s & Company. The enteritidis a n t i s e r u m w a s obtained from t h e Los Angeles County H e a l t h D e p a r t m e n t .
634
T H E JOURNAL OF PEDIATRICS TABL~ I I I
RESULTS OF AGGLUTINATION TES'rS Ws O~GANIS~S OBTAIneD BY ]3LOOD CULTURE. ANTIGEN ORGANISIV[ :PRODUCED IN BLOOD CULTURE DILUTIONS
Antiserum Typhoid Para A P a r a ]9 Enteritidis
1-20 + . + +
40 + . + +
80 + . + +
160 . +
OF
ANTISERUI~S
320 -
640 -
1,280
2,560
5,120
10,240
+
+
+
-~
+
+
20,480
A f t e r t h e r e s u l t s s h o w n in T a b i e Ill/ were obtained, an a g g l u t i n a t i o n t e s t w a s m a d e u s i n g blood s e r u m f r o m the p a t i e n t , with a n a n t i g e n m a d e f r o m a k n o w n p u r e culture of Bacillus enter~tidis. TABLE I V I:{ESULTS OF ~-(]GLUTI1NATIO1N TESTS WITII I=~ATIENT~S BLOOD SERUM. KNOWN PUR]~ CULTURI~ 0!~ B. Enteritid~s
ANTIGEN OF
DILUTION OF SEI%UIv[ Serum Blood s e r u m from patient
1-20 +
40 +
80 +
160 +
320 +
640 +
1,28,0 +
2,560 +
5,120 -
10,240 -
B e c a u s e Bacill~ts entev~tidis is so r a r e l y f o u n d in spinal fluid, a c u l t u r e w a s sent to Dr. K a r l F. M e y e r o f t h e U n i v e r s i t y of California. l i e reported t h e o r g a n i s m to be biochemically a n d serologlcally t y p i c a l Bacill,us enteritidis ( G ~ r t n e r ) . Clinica~ Co~rse.--Fever was p e r s i s t e n t a n d variable, r a n g i n g f r o m 101 ~ F. to 105 ~ F . No d i a r r h e a or a b n o r m a l stools were re)ted. Convulsions were f r e q u e n t , a n d t h e child b e c a m e p r o g r e s s i v e l y weaker u n t i l d e a t h occurred on J u n e 13, 193:l, approxi m a t e l y one m o n t h a f t e r t h e onset. T h e r a p y was l i m i t e d to :frequent spinal d r a i n a g e b y l u m b a r p u n c t u r e , sedatives, a n d f e e d i n g b y g a r a g e . A~topsy.--Dr. C. M. ~Iyland p e r f o r m e d t h e e x a m i n a t i o n on t h e d a y f o l l o w i n g death. T h e b r a i n was swollen, congested, a n d extensively covered b y a p u r u l e n t exudate. The colon showed occasional s m a l l ulcerations of t h e mueosa. T h e s o l i t a r y follicles a n d m e s e n t e r i e l y m p h g l a n d s were hyperplastic. T h e r e m a i n d e r of t h e i n t e s t i n a l t r a c t w a s n e g a t i v e . A n e x u d a t e f o u n d in t h e l e f t m a s t o i d a n t r u m , uns u s p e c t e d cli~fically, yielded Bacillus ente~'itidis on culture. Culture f r o m t h e bowel a t a u t o p s y revealed Bacilluv yogi comm,~ni~.. COMMENT
Thorough study o~ the organism by cultural and serologic methods leaves no doubt as to the correct classification of the offending organism in this patient. The colitis found at autopsy, with the history of diarrhea preceding the onset of meningeal symptoms, suggests that the portal of entry of infection was the intestinal mucosa. The positive blood culture warrants the assumption that the meningeal involvement was metastatic through the blood stream. The finding of Bacillus enteritidis in the mastoid antrum is interesting since the tympanic membranes showed no evidence of middle ear infection during life.
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BACILLUS ENTERITIDIS I'r
635
SUMMAI%u
1. A case of meningitis caused by Bacillus enteritidis of GSrtner is reported in a fifteen-month-old infant. 2. The bacteriologic characteristics of the organism are discussed, and the incidence of causative organisms is given in a series of 100 cases of meningitis in infants and children. To Dr. Phillip E. l%othman, at w~hose suggestion this report was written, I wish to express appreciation of his continued help and interest. I ara indebted to ~Iiss Marion It. Anderson for her technical assistance in the bacteriologic study. REFERENCES 1. 2. 3. 4.
Lynch, F. B , J r , Cooke~ J. V , and Fothergill, L. D., MC Nee, J. W . :
and Shelburne~ S. A.: Am. J. M. Sc. 179: 411, 1930. Bell, ~Ioward ~I.: Am. J. Dis. Child. 24: 387, 1922. and Sweet~ L. K . : J. PEPIAT. 2: 696, 1933. Lancet 1: 218, 1921.
710 WILSHIRE BOULEVAI%D