Reducing Underdiagnosis of Hirschsprung-Associated Enterocolitis: A Novel Scoring System.

BACKGROUND: Hirschsprung-Associated Enterocolitis (HAEC) is a life-threatening and difficult to diagnose complication of Hirschsprung Disease (HSCR). The goal of this study was to evaluate existing HAEC scoring systems and develop a new scoring system. METHODS: Retrospective, multi-institutional data collection was performed. For each patient, all encounters were analyzed. Data included demographics, symptomatology, laboratory and radiographic findings, and treatments received. A "true" diagnosis of HAEC was defined as receipt of treatment with rectal irrigations, antibiotics, and bowel rest. The Pastor and Frykman scoring systems were evaluated for sensitivity/specificity and univariate and multivariate logistic regression performed to create a new scoring system. RESULTS: Four centers worldwide provided data on 200 patients with 1450 encounters and 369 HAEC episodes. Fifty-seven percent of patients experienced one or more episodes of HAEC. Long-segment colonic disease was associated with a higher risk of HAEC on univariate analysis (OR 1.92, 95% CI 1.43-2.57). Six variables were significantly associated with HAEC on multivariate analysis. Using published diagnostic cutoffs, sensitivity/specificity for existing systems were found to be 38.2%/96% for Pastor's and 56.4%/86.9% for Frykman's score. A new scoring system with a sensitivity/specificity of 67.8%/87.9% was created by stepwise multivariate analysis. The new score outperformed the existing scores by decreasing underdiagnosis in this patient cohort. CONCLUSIONS: Existing scoring systems perform poorly in identifying episodes of HAEC, resulting in significant underdiagnosis. The proposed scoring system may be better at identifying those underdiagnosed in the clinical setting. Head-to-head comparison of HAEC scoring systems using prospective data collection may be beneficial to achieve standardization in the field.

Determinants of postoperative abscess occurrence and percutaneous drainage in children with perforated appendicitis.

PURPOSE: Postoperative abscesses after perforated appendicitis have no clear risk factors or indications for percutaneous drainage. Our study addressed these two issues. METHODS: A logistic regression model was used to delineate risk factors for postoperative abscess in children with perforated appendicitis treated during a recent 5-year period. Drainage of abscess was compared to antibiotic treatment. RESULTS: Postoperative abscess occurred in 42 (14.8%) of 284 patients. Higher WBC count, presence of bowel obstruction at presentation, diffuse peritonitis with a dominant abscess at surgery, and one specific surgeon were significantly associated with postoperative abscess, while fever or pain requiring narcotics at the time of abscess diagnosis was significantly associated with drainage. Compared to non-drainage, those drained had longer hospital stay including readmissions (15.9 ± 5.3 vs. 12.2 ± 4.6 days, p < 0.005) and less readmissions (9.5 vs. 33.3%, p = 0.06). Over the 5-year period, there was no increased trend in abscess occurrence (p = 0.56), but there was an increased trend in the use of percutaneous drainage (p = 0.02). CONCLUSIONS: The risk of a postoperative abscess can be predicted by specific clinical characteristics, surgical findings, and treatment-related factors. Percutaneous drainage was associated with longer hospital stays, but less readmissions.

Laparoscopic Sac Disconnection and Peritoneal Closure of Pediatric Inguinal Hernia.

Background: Laparoscopic sac disconnection and peritoneal closure represents an alternative to open pediatric hernia repair. We performed a retrospective review of our data to evaluate this alternative method. Materials and Methods: With REB approval, a retrospective chart review of all patients who underwent laparoscopic indirect inguinal hernia repair between June 2013 and July 2016 was conducted. Primary outcome was the recurrence rate. Secondary outcomes included length of surgery, postoperative hydrocele, and perioperative complications. Data were extracted from EPIC Hyperspace onto a standardized data extraction form. Results: A total of 243 patients were included, of which 82% were males. Age ranged from 1 month to 17 years of age. A total of 322 defects were repaired. Eighty (32%) had contralateral patent processus vaginalis. Twelve (4%) patients presented with incarceration and three (1.2%) had a direct inguinal hernia defect. Recurrence rate was 0.6% (n = 2). There were no intraoperative complications. Operative time was an average of 40 and 54 minutes for unilateral and bilateral repairs, respectively. No testicular ascents, testicular atrophy, vas deferens injury, postoperative hydroceles, and wound infections were reported. Conclusion: Laparoscopic sac disconnection and peritoneal closure of pediatric inguinal hernia is a safe, feasible method with one of the lowest reported recurrence rate among the other laparoscopic methods.

Viral etiologies of lower respiratory tract infections among Egyptian children under five years of age.

BACKGROUND: Lower respiratory tract infections (LRTI) are responsible for a considerable number of deaths among children, particularly in developing countries. In Egypt and the Middle East region, there is a lack of data regarding the viral causes of LRTI. In this study, we aimed to identify the relative prevalence of various respiratory viruses that contribute to LRTIs in young children. Although, nucleic acid-based methods have gained importance as a sensitive tool to determine the viral infections, their use is limited because of their prohibitive cost in low-income countries. Therefore, we applied three different laboratory methods, and presented the different virus prevalence patterns detected by each method. METHODS: We collected nasopharyngeal aspirate samples, demographic data and, clinical data from 450 children under five years of age who presented with LRTI at Abou El Reesh hospital in Cairo during a one-year period. To identify the viral causes of the LRTI we used direct fluorescence assay, real-time reverse-transcriptase polymerase chain reaction (rt-RT-PCR), and shell vial culture. We tested for eight major respiratory viruses. RESULTS: Two hundred sixty-nine patients (59.9%) had a viral infection, among which 10.8% had a co-infection with two or more viruses. By all three methods, respiratory syncytial virus (RSV) was the most predominant, and parainfluenza virus type 2 (HPIV-2), influenza B virus (FLUBV) were the least predominant. Other viral prevalence patterns differed according to the detection method used. The distribution of various viruses among different age groups and seasonal distribution of the viruses were also determined. CONCLUSIONS: RSV and human adenovirus were the most common respiratory viruses detected by rt-RT-PCR. Co-infections were found to be frequent among children and the vast majority of co-infections were detected by nucleic acid-based detection assays.

Is horseshoe lung a component of VACTERL spectrum? Case report and review of literature.

Horseshoe lung (HL) is a rare congenital anomaly that has been classically associated with Scimitar syndrome. Very few cases have been described in the context of the VACTERL spectrum. We present a case of a newborn girl with mesocardia, tracheoesophageal fistula, and imperforated anus, who required O2 support at birth and during hospitalization. A chest CT angiography revealed a HL as an incidental finding. We suspect that HL and the VACTERL spectrum, are not separated entities but likely a further expansion of VACTERL-associated symptoms. HL might be underdiagnosed in asymptomatic patients as Chest CT angiography is not part of the routine work up for patients with VACTERL association.

The utility of magnetic resonance imaging in the diagnosis and management of pediatric benign ovarian lesions.

BACKGROUND: The utility of magnetic resonance imaging (MRI) in the diagnosis and management of pediatric ovarian lesions has not been well defined. METHODS: A retrospective review of all girls who underwent MRI evaluation of ovarian masses during the period 2009-2015 was performed. The accuracy of MRI was evaluated by comparing results with surgical findings, pathology reports, and subsequent imaging. The influence of the MRI on the treatment plan was specifically explored. RESULTS: Eighteen girls, 12-17years of age, underwent 27 MRIs, subsequent to ultrasound identification of ovarian lesions. Of 9 neoplastic lesions diagnosed on MRI, 8 (89%) were confirmed by surgical and pathological findings. Of 18 functional lesions, 17 (94.4%) were confirmed pathologically or by resolution on subsequent imaging. Twenty MRI exams (74%) directly influenced the treatment plan, by leading to appropriate operative intervention in 9 and appropriate observation in 11. The extent of ovarian resection was guided by MRI findings in 8 of 9 (89%) neoplastic lesions. For characterizing lesions as neoplastic, the sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of MRI were 89%, 94%, 94%, 89%, and 93% respectively. CONCLUSIONS: MRI can differentiate functional from neoplastic pediatric ovarian masses, and guide ovarian resection in appropriate cases. LEVEL OF STUDY: II.

Risk stratification in pediatric perforated appendicitis: Prospective correlation with outcomes and resource utilization.

PURPOSE: Despite a wide spectrum of severity, perforated appendicitis in children is typically considered a single entity in outcomes studies. We performed a prospective cohort study to define a risk stratification system that correlates with outcomes and resource utilization. METHODS: A prospective study was conducted of all children operated for perforated appendicitis between May 2015 and December 2016 at a tertiary free-standing university children's hospital. Surgical findings were classified into one of four grades of perforation: I. localized or contained perforation, II. Contained abscess with no generalized peritonitis, III. Generalized peritonitis with no dominant abscess, IV. Generalized peritonitis with one or more dominant abscesses. All patients were treated on a clinical pathway that involved all points of care from admission to final follow-up. Outcomes and resource utilization measures were analyzed using Fisher's exact test, Kruskal-Wallis test, One-way ANOVA, and logistic regression. RESULTS: During the study period, 122 patients completed treatment, and 100% had documented follow-up at a median of 25days after operation. Grades of perforation were: I, 20.5%; II, 37.7%; III, 10.7%; IV, 31.1%. Postoperative abscesses occurred in 12 (9.8%) of patients, almost exclusively in Grade IV perforations. Hospital stay, duration of antibiotics, TPN utilization, and the incidence of postoperative imaging significantly increased with increasing grade of perforation. CONCLUSION: Outcomes and resource utilization strongly correlate with increasing grade of perforated appendicitis. Postoperative abscesses, additional imaging, and additional invasive procedures occur disproportionately in patients who present with diffuse peritonitis and abscess formation. The current stratification allows risk-adjusted outcome reporting and appropriate assignment of resource burden. LEVEL OF EVIDENCE: I (Prognosis Study).

Appropriate use of total parenteral nutrition in children with perforated appendicitis.

BACKGROUND: Total parenteral nutrition (TPN) is often used in children with perforated appendicitis, despite the absence of clear indications. We assessed the validity of specific clinical indications for initiation of TPN in this patient cohort. METHODS: Data were gathered prospectively on duration of nil per os (NPO) status and TPN use in a cohort of children treated under a perforated appendicitis protocol during a 19-month period. TPN was started in the immediate postoperative period in patients who had generalized peritonitis and severe intestinal dilatation at operation, or later per the discretion of the attending surgeon. At discharge, TPN was considered to have been used appropriately, according to consensus guidelines, if the patient was NPO≥7days or received TPN≥5days. RESULTS: During the study period, TPN was initiated in 31 (25.4%) of 122 patients operated for perforated appendicitis. Sixteen (51.6%) received TPN per operative finding indications and 15 (48.4%) for prolonged ileus. The operative indications demonstrated 47% sensitivity, 86% specificity, a positive predictive value (PPV) of 35%, and a negative predictive value (NPV) of 91%, when adherence to TPN consensus guidelines was considered the gold standard. CONCLUSION: Patients without severe intestinal dilatation and generalized peritonitis at operation should not be placed on TPN in the immediate postoperative period. Refinement of selection criteria is necessary to further decrease inappropriate TPN use in children with perforated appendicitis. TYPE OF STUDY: Diagnostic Test. LEVEL OF STUDY: II.

Determinants of outcomes in patients with simple gastroschisis.

PURPOSE: We analyzed the determinants of outcomes in simple gastroschisis (GS) not complicated by intestinal atresia, perforation, or necrosis. METHODS: All simple GS patients enrolled in a national prospective registry from 2005 to 2013 were studied. Patients below the median for total parenteral nutrition (TPN) duration (26days) and hospital stay (34days) were compared to those above. Univariate and multivariate logistic and linear regression analyses were employed using maternal, patient, postnatal, and treatment variables. RESULTS: Of 700 patients with simple GS, representing 76.8% of all GS patients, 690 (98.6%) survived. TPN was used in 352 (51.6%) and 330 (48.4%) patients for ≤26 and >26days, respectively. Hospital stay for 356 (51.9%) and 330 (48.1%) infants was ≤34 and >34days, respectively. Univariate analysis revealed significant differences in several patient, treatment, and postnatal factors. On multivariate analysis, prenatal sonographic bowel dilation, older age at closure, necrotizing enterocolitis, longer mechanical ventilation, and central-line associated blood stream infection (CLABSI) were independently associated with longer TPN duration and hospital stay, with CLABSI being the strongest predictor. CONCLUSIONS: Prenatal bowel dilation is associated with increased morbidity in simple GS. CLABSI is the strongest predictor of outcomes. Bowel matting is not an independent risk factor. LEVEL OF EVIDENCE: 2c.

Loop versus divided colostomy for the management of anorectal malformations: a systematic review and meta-analysis.

BACKGROUND: The ideal colostomy type for patients with anorectal malformations (ARM) is undetermined. We performed a systematic review and meta-analysis of short-term complications comparing loop and divided colostomies. METHODS: After review registration (PROSPERO: CRD42016036481), multiple databases were searched for comparative studies without language or date restrictions. Gray literature was sought. Complications investigated included stomal prolapse/hernia/retraction, wound infections, and urinary tract infections (UTIs). Two reviewers independently assessed study eligibility and the quality of included studies. Meta-analysis of selected complications was performed using Revman 5.3, with p<0.05 considered significant. RESULTS: Twenty-six studies were included, and four were multi-institutional. Reporting standards were highly variable. Studies scored between 6 and 9 of possible nine stars on the NOS. Overall, 3866 neonates with ARM were incorporated, in which 2241 loop colostomies and 1994 divided colostomies were reported. Of 10 studies reporting short-term complications, the overall rate was 27%. Meta-analysis demonstrated no significant difference in the incidence of UTIs, (OR: 2.55 [0.76, 8.58], p=0.12), while loop colostomies had a significantly higher prolapse rate (See figure). No publication bias was noted. CONCLUSIONS: A colostomy for patients with an ARM is a source of considerable morbidity. Divided colostomies reduce the risk of subsequent prolapse and may represent the preferred approach. LEVEL OF EVIDENCE: 3A.

Standardization of care for pediatric perforated appendicitis improves outcomes.

BACKGROUND: The treatment of perforated appendicitis in children is characterized by significant variability in care, morbidity, resource utilization, and outcomes. We prospectively studied how minimization of care variability affects outcomes. METHODS: A clinical pathway for perforated appendicitis, in use for three decades, was further standardized in May 2015 by initiation of a disease severity classification, refinement of discharge criteria, standardization of the operation, and establishment of criteria for use of postoperative total parenteral nutrition, imaging, and invasive procedures. Prospective evaluation of all children treated for 20months on the new fully standardized protocol was conducted and compared to a retrospective cohort treated over 58months prior to standardization. Differences between outcomes before and after standardization were analyzed using regression analysis techniques to adjust for disease severity. RESULTS: Median follow-up time post discharge was 25 and 14days in the post- and prestandardization groups, respectively. Standardization significantly reduced postoperative abscess (9.8% vs. 17.4%, p=0.001) and hospital stay (p=0.002). Standardization reduced the odds of developing a postoperative abscess by four fold. CONCLUSION: Minimizing variability of care at all points in the treatment of perforated appendicitis significantly improves outcomes. TYPE OF STUDY: Prospective Cohort Study. LEVEL OF EVIDENCE: Level II.

Differentiation of tuberculous meningitis from acute bacterial meningitis using simple clinical and laboratory parameters.

Tuberculous meningitis (TBM) is still a major cause of serious illness in many parts of the world. The newer diagnostic tests and neuroimaging methods are unlikely to be available in many developing countries. We attempt to identify simple parameters for early diagnosis. A retrospective study was performed to compare the clinical and laboratory features of cultured-confirmed, TBM (134) and other bacterial meningitis (709). Features independently predictive of TBM were studied by multivariate logistic regression to develop a diagnostic rule. Six features were found predictive: length of clinical history >5 days, headache, total cerebrospinal fluid (CSF) white blood cell count of <1000/mm3, clear appearance of CSF, lymphocyte proportion of >30%, and protein content of >100 mg/dL. Application of 3 or more parameters revealed 93% sensitivity and 77% specificity. Applying this diagnostic rule can help in the early diagnosis of TBM, in both children and adults.

Enteric pathogens associated with diarrhea in children in Fayoum, Egypt.

In a cross-sectional study of children <60 months old from Fayoum, Egypt, presenting with diarrhea, 46% (162/356) had detectable enteric pathogens. Bacterial pathogens were identified in 25% (89/356), whereas rotavirus and Cryptosporidium were detected in 21% (54/253) and 15% (39/253), respectively. Cryptosporidium is an important pathogen in this region.

Gastroschisis outcomes in North America: a comparison of Canada and the United States.

BACKGROUND: Care of infants with gastroschisis is centralized in Canada and noncentralized in the United States. We conducted an outcomes comparison between the two countries and analyzed the determinants of such outcomes. METHODS: Inpatient mortality and hospital stay of gastroschisis patients from the Canadian Pediatric Surgery Network prospective clinical database for the period 2005-2013 were compared with those from the US Kids Inpatient Database for the period 2003-2012. Potential outcome determinants were analyzed using univariate and multivariate analyses. RESULTS: A comparison was made between 695 Canadian patients and 5216 American patients. Complex gastroschisis was found in 16.0% and 13.7% of patients in Canada and the US, respectively; P=0.11. Canada had less premature births, more normal birth weight (BW) infants, less cesarean section deliveries, and more inborn patients compared to the US. For simple gastroschisis, Canadian mortality was lower (1.4% vs. 3.4%; P=.008) and hospital stay was longer (45±38 vs. 41±32days; P=.04). US mortality correlated strongly with low BW (P=.002) and marginally with cesarean section delivery (P=.08). A longer Canadian hospital stay was associated with lower gestational age (P=0.01) and western region (P=0.04), while a longer American hospital stay was associated with medium neonatal intensive care unit gastroschisis volume (P=.03), low socioeconomic status (P=.06), low BW (P=0.06), and public insurance (P=0.07). Outcomes for complex gastroschisis did not differ between Canada and the US. CONCLUSIONS: Mortality for simple gastroschisis is higher in the US than in Canada, whereas no outcome differences exist for complex gastroschisis. Outcome determinants are different between the 2 countries.

Flap versus fascial closure for gastroschisis: a systematic review and meta-analysis.

BACKGROUND: Flap closure represents an alternative to fascial closure for gastroschisis. We performed a systematic review and meta-analysis of outcomes comparing these techniques. METHODS: A registered systematic review ( PROSPERO: CRD42015016745) of comparative studies was performed, querying multiple databases without language or date restrictions. Gray literature was sought. Outcomes analyzed included: mortality, ventilation days, feeding parameters, length of stay (LOS), wound infection, resource utilization, and umbilical hernia incidence. Multiple reviewers independently assessed study eligibility and literature quality. Meta-analysis of outcomes was performed where appropriate (Revman 5.2). RESULTS: Twelve studies met inclusion criteria, of which three were multi-institutional. Quality assessment revealed unbiased patient selection and exposure, but group comparability was suboptimal in four studies. Overall, 1124 patients were evaluated, of which 350 underwent flap closure (210 immediately; 140 post-silo). Meta-analysis revealed no significant differences in mortality, LOS, or feeding parameters between groups. Flap patients had less wound infections (OR 0.40 [95%CI 0.22-0.74], P=0.003). While flap patients had an increased risk of umbilical hernia, they were less likely to undergo repair (19% vs. 41%; P=0.01). CONCLUSIONS: Flap closure has equivalent or superior outcomes to fascial closure for patients with gastroschisis. Given potential advantages of bedside closure and reduced sedation requirements, flap closure may represent the preferred closure strategy.

Hospital-based surveillance for acute febrile illness in Egypt: a focus on community-acquired bloodstream infections.

Acute febrile illness (AFI) is a common syndrome in Egypt. However its etiologies are not well characterized. To determine the relative frequency of pathogen etiologies and possibly improve diagnostic, clinical management and public health measures, we implemented laboratory-based surveillance in a network of infectious disease hospitals throughout Egypt. Admitted patients with AFI provided background details and a blood sample for bacterial culture and serologic analysis. Case definitions were based on laboratory results. Of 10,130 patients evaluated between 1999 and 2003, 5% were culture positive for Salmonella enterica serogroup Typhi, 3% for Brucella, and 2% for other pathogens. An additional 18% of patients had positive serologic results for typhoid and 11% for brucellosis. Risk factor analysis identified availability of municipal water to be significantly (P < 0.05) associated with protection against typhoid. Animal contact and consumption of raw dairy products were significantly associated with brucellosis. The surveillance network identified typhoid fever and brucellosis as the most common bacterial causes of AFI in Egypt, allowed better description of their epidemiology, and may lead to the development of targeted prevention strategies.

The correlation between the time spent in utero and the severity of bowel matting in newborns with gastroschisis.

BACKGROUND: Optimal timing of delivery in fetuses with gastroschisis (GS) is unknown. Some favor early induced delivery to prevent bowel injury. This study evaluates the correlation between bowel injury and the gestational age at birth using the Gastroschisis Prognostic Score (GPS). METHODS: A national database was analyzed from 2005 to 2013. Patients were pooled based on their gestational age at birth. The mean GPS and % of patients with severe bowel matting were tabulated for each week in utero. Regression modeling was used to evaluate the relationship between the dependent (severe matting and GPS) and independent (gestational age) variables and the R(2) coefficient of determination was derived to evaluate model strength. Additional factors influencing the timing of delivery were evaluated. RESULTS: Of 780 cases, 88 were excluded because of missing data. A linear relationship is seen between increasing gestational age and decreasing bowel matting (R(2)=0.66) and GPS (R(2)=0.72). For every week in utero, the % of patients with severe matting decreases by 3.6%. CONCLUSION: Early induced delivery simply to protect the bowel from ongoing in utero damage appears unfounded and should be reserved for evidence of closing gastroschisis or traditional obstetrical/fetal indications.

A risk-stratified comparison of fascial versus flap closure techniques on the early outcomes of infants with gastroschisis.

BACKGROUND: While fascial closure is traditionally used in gastroschisis (GS), flap closure (skin or umbilical cord) has gained popularity. We evaluated early outcomes and complications of the two techniques. METHODS: A national, population-based gastroschisis data registry was analyzed from 2005 to 2011. We compared fascial to flap closures and stratified patients into low or high-risk groups using the Gastroschisis Prognostic Score (GPS), a validated marker of post-natal bowel injury. Demographic and outcome data, including length of stay, complications, and markers of resource utilization were analyzed using Fisher's exact and Student's t-tests for categorical and continuous variables, respectively (p<0.05 significant). RESULTS: The analyzed dataset included 436 fascial closures (344 [78.8%] low-risk, 92 high-risk) and 129 flap closures (112 [86.7%] low-risk, 17 high-risk; p=0.06). Demographics and birth weight did not differ between groups. In patients with low GPS, flap closure demonstrated significant decreases in resource utilization and failure of closure, without differences in complication rates. Analysis of high-risk patients revealed no statistically significant differences in outcome. CONCLUSION: Flap closure was not associated with an increase in patient morbidity and seemed suitable as a definitive closure method for gastroschisis patients irrespective of disease severity. Furthermore, flap closure reduced several markers of resource utilization in patients with low-risk disease.

Etiology, antimicrobial susceptibility profiles, and mortality associated with bacterial meningitis among children in Egypt.

PURPOSE: Surveillance for patients with meningitis is a high priority in order to determine the etiology of disease and design prevention strategies. This study presents data on the causes of bacterial meningitis among children <6 years of age treated in a network of hospitals throughout Egypt. METHODS: Training was provided to standardize the collection of clinical information and optimize recovery of bacterial pathogens. Bacterial isolates were tested for antimicrobial resistance patterns using Kirby Bauer disk diffusion, E-test and/or Beta-lactamase (BL) testing methods. RESULTS: Patients with culture-confirmed bacterial meningitis (228 children<6 years) were identified including 89 (39%) patients with H. influenzae (HI), 68 (30%) with Streptococcus pneumoniae (SP), 30 (13%) with N. meningitidis (NM), 18 (8%) with Mycobacterium tuberculosis (MTB) and 23 (10%) with other bacteria. The overall case fatality ratio was high (24%) and increased among children with TB meningitis (56%). The susceptibility for HI to ampicillin (AMP), chloramphenicol (C) and ceftriaxone (CRO) was 21%, 13%, and 100% respectively. The susceptibility for SP to C and CRO was 79% and 100%, respectively. CONCLUSIONS: HI and SP are the leading causes of bacterial meningitis among children in Egypt. The majority of HI strains tested were resistant to AMP or C suggesting the need for routine use of CRO as first line therapy. Among older children TB emerges as a significant cause of bacterial meningitis in Egypt.

Introductory evaluation of an oral, killed whole cell enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine in Egyptian infants.

BACKGROUND: We conducted the first trial to assess the safety and immunogenicity of an oral, killed enterotoxigenic Escherichia coli plus cholera toxin B-subunit vaccine in children <2 years old. METHODS: Three doses of vaccine or killed E. coli K-12 control were given at 2-week intervals to 64 Egyptian infants, 6 to 18 months old, in a randomized, double blind manner. Adverse events were monitored for 3 days after each dose. Blood was collected before immunization and 7 to 10 days after each dose to assess vaccine-specific serologic responses. RESULTS: There was no statistically significant intergroup difference in the percentage of subjects reporting the primary safety endpoint (diarrhea or vomiting) after the first (31%, vaccine; 30%, control) or third (14%, vaccine; 18%, control) dose, whereas there was a trend toward greater reporting in the vaccine group after Dose 2 (36%, vaccine; 18%, control; P = 0.052). The percentage of children showing IgA seroconversion after any dose was higher in the vaccine than the control group for recombinant cholera toxin B-subunit (97% vs. 46%), colonization factor antigen I (61% vs. 18%) and coli surface antigen 4 (39% vs. 4%) (P < 0.001 for each comparison). IgG seroconversion rates in the vaccine and control groups were 97 and 21% to recombinant cholera toxin B-subunit (P < 0.001), 64 and 29% for colonization factor antigen I (P < 0.01), 53 and 21% for coli surface antigen 2 (P < 0.05) and 58 and 4% for coli surface antigen 4 (P < 0.001), respectively. The third vaccine dose was followed by augmented IgG antitoxin titers. CONCLUSION: The oral enterotoxigenic E. coli vaccine was safe and immunogenic in this setting in Egyptian infants.