Central nervous system manifestations of childhood shigellosis: Prevalence, risk factors, and outcome

Background and Objective. Alterations in consciousness, including seizures, delirium, and coma, are known to occur during Shigella infection. Previous reports have suggested that febrile convulsions and altered consciousness are more common during shigellosis than with other childhood infections. Th ose reports, however, have been from locations where S dysenteriae type 1 w as not common, thus making it difficult to assess the specific contribution that S dysenteriae type 1 infection, and Shiga toxin, might make to the pa thogenesis of altered consciousness in children with shigellosis. In this s tudy we seek to determine the prevalence, risk factors, and outcome of alte red consciousness in children with shigellosis in Bangladesh, a country whe re infection with all four species of Shigella is common. We particularly f ocus on the importance of metabolic abnormalities, which we have previously shown to be a common feature of shigellosis in this population. Methods. This study was conducted at the Diarrhea Treatment Centre of the I nternational Centre for Diarrhoeal Disease Research, Bangladesh in Dhaka, B angladesh, which provides care free of charge to persons with diarrhea. Dur ing 1 year, a study physician identified all inpatients infected with Shige lla by checking the logs of the Clinical Microbiology Laboratory daily. Stu dy physicians obtained demographic and historical information by reviewing the patient charts and by interviewing patients, or their parents or guardi ans, to confirm or complete the history of illness obtained on admission. P atients were categorized as being conscious or unconscious based on a clini cal scale; having a seizure documented in the hospital; or having a seizure by history during the current illness that was not witnessed by medical pe rsonnel. Patient outcome was classified as discharged improved, discharged against medical advice, transferred to another health facility, or died in the Treatment Centre. Laboratory examinations were ordered at the discretio n of the attending physician; all such information was recorded on the stud y form. Clinical management was by the attending physician. Factors indepen dently predictive of a documented seizure, or of unconsciousness, were dete rmined using a multiple logistic regression analysis. For this analysis var iables associated with unconsciousness or a documented seizure in the analy sis of variance or chi(2) analyses were entered into the regression equatio n and eliminated in a backward stepwise fashion if the probability associat ed with the likelihood ratio statistic exceeded .10. Results. During this 1-year study, 83 402 persons with diarrhea came to the Treatment Centre for care, and 6290 patients were admitted to the inpatien t unit. Shigella was isolated from a stool or rectal swab sample of 863 (13 .7%) of the inpatients. Seventy-one (8%) of the inpatients with shigellosis were greater than or eq ual to 15 years old; 61 (86%) were conscious; 10 (14%) were unconscious; no ne had either a documented seizure or a seizure by history during this illn ess. Seven hundred ninety-two patients were <15 years old (92%); 654 (83%) were conscious; 73 (9%) were unconscious; 41 (5%) had a documented seizure (compared with greater than or equal to 15-year age group); 24 (3%) had a s eizure by history during this illness. Of the 41 patients with documented s eizures, 19 (46.3%) had a seizure at the time of admission, and 22 (53.7%) had a seizure after admission. Twenty-five (61.0%) of the 41 patients with documented seizures were reported to have a seizure during this illness bef ore coming to the Treatment Centre. Clinical features that are known to cause altered consciousness-fever, seve re dehydration, hypoglycemia, hyponatremia, or meningitis-were present in 3 8 (92.7%) of the 41 patients in whom a seizure was witnessed and in 67 (91. 8%) of the 73 patients who were unconscious. Nineteen (46.3%) of the patien ts who had a seizure documented had two of these five features, 4 (9.8%) ha d three, and 1 (2.4%) had four of these features; among unconscious patient s two of the features were present in 25 (34.2%) and three in 2 (2.7%). In a multiple regression analysis factors independently associated with a docu mented seizure in patients <15 years old were a shorter duration of diarrhe a, higher body temperature, higher median weight-for-age, increased proport ion of immature leukocytes, higher serum potassium, and lower serum sodium. Factors associated with unconsciousness were older age, a shorter duration of diarrhea, higher admission temperature, severe dehydration, and higher serum potassium. In the multiple logistic regression analysis we found no a ssociation between the infecting species of Shigella and either the occurre nce of seizures or altered consciousness. Patients who were unconscious (death rate 48%) or had a documented seizure (death rate (29%) were at significantly increased risk of death compared wi th conscious patients (death rate 6%) or patients who had a seizure by hist ory (no deaths). There were no deaths among patients 15 years or older. Conclusions. This study had a substantially larger number of patients than any of the previously published clinical studies on seizures or altered con sciousness during shigellosis. The results of this study suggest that seizu res in shigellosis in the population studied occur in an age group-children 5 years of age or less-known to be at increased risk of seizures from feve r or metabolic alterations. This study also suggests that, at least in the majority of these inpatients, altered consciousness is not related to Shiga toxin, which is produced in appreciable amounts only by the S dysenteriae type I serotype. Direct infection of the central nervous system also was no t a major cause of altered consciousness in these patients. Both diminished consciousness and documented seizures are associated with a poor outcome i n Bangladeshi children with shigellosis. Prompt attention to fever reductio n and metabolic alterations may help reduce these potentially lethal compli cations, but often this is not easy to accomplish in the poor countries whe re shigellosis is endemic.