Central Nervous System Manifestations of Childhood Shigellosis: Prevalence, Risk Factors, and Outcome

Abstract

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. Those reports, however, have been from locations where S dysenteriae type 1 was not common, thus making it difficult to assess the specific contribution that S dysenteriae type 1 infection, and Shiga toxin, might make to the pathogenesis of altered consciousness in children with shigellosis. In this study we seek to determine the prevalence, risk factors, and outcome of altered consciousness in children with shigellosis in Bangladesh, a country where infection with all four species of Shigella is common. We particularly focus 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 International Centre for Diarrhoeal Disease Research, Bangladesh in Dhaka, Bangladesh, which provides care free of charge to persons with diarrhea. During 1 year, a study physician identified all inpatients infected withShigella by checking the logs of the Clinical Microbiology Laboratory daily. Study physicians obtained demographic and historical information by reviewing the patient charts and by interviewing patients, or their parents or guardians, to confirm or complete the history of illness obtained on admission. Patients were categorized as being conscious or unconscious based on a clinical scale; having a seizure documented in the hospital; or having a seizure by history during the current illness that was not witnessed by medical personnel. 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 discretion of the attending physician; all such information was recorded on the study form. Clinical management was by the attending physician. Factors independently predictive of a documented seizure, or of unconsciousness, were determined using a multiple logistic regression analysis. For this analysis variables associated with unconsciousness or a documented seizure in the analysis of variance or χ2 analyses were entered into the regression equation and eliminated in a backward stepwise fashion if the probability associated 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 inpatient 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 ≥15 years old; 61 (86%) were conscious; 10 (14%) were unconscious; none had either a documented seizure or a seizure by history during this illness. 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 ≥15-year age group); 24 (3%) had a seizure by history during this illness. Of the 41 patients with documented seizures, 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 before coming to the Treatment Centre. Clinical features that are known to cause altered consciousness—fever, severe dehydration, hypoglycemia, hyponatremia, or meningitis—were present in 38 (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 patients who had a seizure documented had two of these five features, 4 (9.8%) had three, and 1 (2.4%) had four of these features; among unconscious patients 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 documented seizure in patients <15 years old were a shorter duration of diarrhea, higher body temperature, higher median weight-for-age, increased proportion 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 association between the infecting species ofShigella and either the occurrence 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 with conscious patients (death rate 6%) or patients who had a seizure by history (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 consciousness during shigellosis. The results of this study suggest that seizures 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 fever 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 1 serotype. Direct infection of the central nervous system also was not a major cause of altered consciousness in these patients. Both diminished consciousness and documented seizures are associated with a poor outcome in Bangladeshi children with shigellosis. Prompt attention to fever reduction and metabolic alterations may help reduce these potentially lethal complications, but often this is not easy to accomplish in the poor countries where shigellosis is endemic.