Chantal Buteau

Leukocytosis in children with Escherichia coli O157:H7 enteritis developing the hemolytic-uremic syndrome.

Background. Fewer than 10% of children with Escherichia coli O157:H7 enteritis develop hemolytic‐uremic syndrome (HUS). Objective. To determine whether circulating leukocytes are independent risk markers of developing HUS during E. coli O157:H7 enteritis. Methods. We reviewed the charts of all children with culture‐proved E. coli O157:H7 infections seen at Sainte‐Justine Hospital between 1987 and 1997. Epidemiologic data, laboratory indices and circulating leukocytes counts were noted. HUS diagnosis was validated with independent HUS patient lists from the pediatric nephrology services of tertiary care hospitals in the Montreal metropolitan area. The date of onset of enteritis was determined by two independent observers. Leukocyte counts were compared among the following independent groups: (1) uncomplicated O157:H7 enteritis (Group 1); (2) O157:H7 enteritis with the subsequent development of HUS (Group 2); (3) HUS already present at the time of medical consultation (Group 3). Results. There were 369 children with E. coli O157:H7 infection. A complete blood count was not performed in 114 (31%) patients. Observers disagreed on the date of onset of gastroenteritis in 34 (9%) children only (kappa 0.92). The study population thus included 221 patients: Group 1, n = 161; Group 2, n = 27; and Group 3, n = 33. Patients developing HUS (Group 2) presented greater total leukocyte (P < 0.008), polymorphonuclear (P < 0.008) and monocyte (P < 0.07) counts than those with an uncomplicated course (Group 1). Logistic regression analysis showed that young age [odds ratio (OR), 0.98; 95% confidence interval (CI), 0.96 to 0.99], duration of enteric prodrome ≤3 days (OR 4.8, 95% CI 1.13 to 20.7) and initial leukocytosis (OR 1.22, 95% CI, 1.11 to 1.35) were independent predictors of HUS. Conclusions. Based on the variables identified above, further studies are needed to determine whether the inflammatory response of the host represents only a marker of the severity of gastrointestinal infection or whether, alternatively, it is a pathophysiologic factor that leads to HUS.

Deep cutaneous fungal infections in immunocompromised children

BACKGROUND Life-threatening infections from ubiquitous fungi are becoming more prevalent in adults and children because of the increased use of immunosuppressive agents and broad-spectrum anti-infective drugs. Extremely low birth weight premature neonates and patients with a disrupted epidermal barrier are also at increased risk. Lethality is high, particularly with delayed diagnosis. As cutaneous lesions are often the first manifestation of such infections, early recognition of suspicious lesions is crucial to decrease associated morbidity and mortality. The clinical features of deep cutaneous fungal infection (DCFI) in immunocompromised children deserve special attention. OBJECTIVES This study aimed to characterize our pediatric patients with DCFI, the causative fungi, and the associated risk factors. METHODS A medical record review was conducted of pediatric patients with DCFI treated at out institution using data retrieved from the hospitals pathology and microbiology database (1980-2008). RESULTS In all, 26 patients with DCFI were identified (9 girls and 17 boys) ranging in age from 1 day to 18 years (mean age: 8 years), the majority of whom had a hematologic disorder. All patients were immunocompromised, 90% were receiving broad-spectrum antibiotics, and 50% had severe neutropenia (absolute neutrophilic count < or = 500 x 10(6)/L). Necrotic ulcers (42%) and papules (34%) represented the most frequent lesion morphology. Fungal species were identified by culture in 20 (87%) of 23 patients tested and were observed histopathologically in 20 of 23 patients tested. Aspergillus was identified in 12 (44%) patients and Candida in 9 (33%). The other species included Fusarium (one), Exserohilum rostratum (one), Alternaria (one), Zygomycetes (two), and Blatomycetes (one). All but two patients received systemic antifungal therapy; wide surgical excision was performed in 13. Infection resolved in 20 (77%), whereas 6 (23%) died of disseminated infection. LIMITATIONS This study was limited by the small number of cases and the retrospective nature of the collected data. DISCUSSION DCFI should rank high in the differential diagnosis of any suspicious skin lesions in immunocompromised children. Early biopsies should be performed for histopathology and microbiological analysis, as lethality is high if appropriate treatment is delayed.

Is routine chest radiography necessary for the initial evaluation of fever in neutropenic children with cancer

The yield of routine chest radiography (CXR) as part of the initial management of febrile neutropenic pediatric oncology patients is questionable.

Systemic capillary leak syndrome presenting as recurrent shock.

Objective: To report a case of systemic capillary leak syndrome (SCLS) in a child. Design: Case report. Setting: Pediatric intensive care unit. Patient: A 6-yr-old girl was admitted twice to the pediatric intensive care unit, at a 10-month interval, in severe shock with important edema. Results: The patient presented with acute symptoms of abdominal pain, vomiting, and syncope in the hour preceding the shock. During both episodes necessary management included aggressive intravenous fluid rehydration, mechanical ventilation, and use of inotropes/vasopressors. Suspicion of a lower limb fasciitis necessitated surgical exploration, but pathology reports were negative on both occasions revealing only subcutaneous tissue edema. The patient recovered within 24 hrs on both episodes. Investigation ruled out cardiogenic shock and septic shock due to bacterial etiology. On the first episode, a nasopharyngeal aspirate was positive for influenza A (H3N2) by both viral immunofluorescence and culture. The presumed diagnosis was toxic shock syndrome associated with influenza virus. On the second episode, all bacterial and virology cultures remained negative. Hypovolemic shock was suspected, but there was no history of dehydration, bleeding, or gastrointestinal losses (persistent vomiting or diarrhea). Noninfectious causes of hypovolemic shock with edema were ruled out, leading us to believe that she suffered from SCLS. Conclusions: Although well described in the adult literature, there have been few reports of SCLS in pediatric patients. SCLS should be considered in the differential diagnosis of recurrent hypovolemic shock without identifiable cause. The only therapeutic intervention is to obtain vascular access when initial manifestations occur and give aggressive fluid reanimation.

Prevention of CMV disease in pediatric kidney transplant recipients: Evaluation of pp67 NASBA-based pre-emptive ganciclovir therapy combined with CMV hyperimmune globulin prophylaxis in high-risk patients

Abstract:  A new prevention strategy for CMV infection was evaluated in our pediatric kidney transplant unit. This approach comprises a pre‐emptive therapy, based upon the monitoring of CMV pp67 mRNA in whole blood by the qualitative NASBA, combined with prophylactic CMV‐IG in high risk (R−/D+) children. Thirty‐one kidney transplant children were followed for six months with serial measurements of CMV pp67 mRNA in the blood. The R−/D+ patients were given prophylactic CMV‐IG for the first 16 wk after transplantation. I.v. ganciclovir was administered upon CMV detection by NASBA and was discontinued after two consecutive negative results. CMV infection, detected by NASBA, developed in 11 (35%) recipients: one (33%) of the R+/D− patients and 10 (72%) of the R−/D+ patients. CMV disease developed in 9.6% of the patients (3/31), exclusively in the R−/D+ group. These three patients presented concurrently with CMV viremia and disease. It is noteworthy that two of the three patients could not receive a complete course of CMV‐IG, and one of the latter two subjects had been treated for acute rejection 15 days before CMV infection. Ganciclovir was given for the 11 cases of primary infection, and for three cases of relapsed CMV infection. pp67 NASBA‐based pre‐emptive ganciclovir therapy, combined with prophylactic CMV‐IG in high‐risk patients leads to a lower rate of CMV disease, as long as a complete course of CMV‐IG has been administered and ganciclovir is given during the period of treatment for acute rejection in high‐risk populations.

Infectious risk in pediatric organ transplant recipients: Is it increased with the new immunosuppressive agents?

Abstract:  The risk of infection in pediatric organ transplant recipients is determined by several factors, including age, the types of organ transplanted and the immunosuppressive treatment which has dramatically changed over the past 10 yr. Little information has been reported regarding the infectious complications related to the current immunosuppressive protocols used in these children. This paper reviews (i) the immunosuppressive agents, focusing on their mechanisms of action and on the new regimens, (ii) the infections related to excessive immunosuppression and also anti‐infectious properties or infectious adverse reactions associated with specific immunosuppressive agents. With the new immunosuppressive protocols, the advances in immunologic monitoring, microbiological diagnosis, anti‐infectious prophylactic and preemptive treatments, strategies to minimize the risk of infection related to the immunosuppressive therapy are proposed.

Transfusion-related Epstein-Barr virus infection among stem cell transplant recipients: a retrospective cohort study in children

BACKGROUND: Blood safety warrants strict screening measures to minimize the risk of transmitting blood‐borne pathogens. However, transfusion‐transmitted infections for which testing is not currently performed continue to be a concern. Among these untested agents is Epstein‐Barr virus (EBV) which, in the transplant setting, is associated with lymphoproliferative disease, a potentially fatal cancer. The aim of this study was to analyze the incidence of posttransplant EBV infection and its association with administration of blood products in children receiving a hematopoietic stem cell (HSC) graft.

Fatal cases of Staphylococcus aureus pleural empyema in infants.

Community-associated infections and especially pleural empyema due to Staphylococcus aureus are increasing worldwide. The virulence of staphylococcal strains is notably determined by different toxin expressing–genes, such as the Panton-Valentine leukocidin (PVL) gene found in S. aureus isolates obtained from pediatric necrotizing pneumonia samples. We describe 2 similar cases of infants with severe respiratory distress and death after an upper respiratory tract infection, having occurred in the same urban area during the same winter time. Necropsies performed between November 2006 and March 2007 revealed bronchopneumonia and an important pleural empyema, justifying the review of clinical charts and laboratory exams. A methicillin-sensitive S. aureus (MSSA) isolate carrying the PVL gene was identified in both cases. We have subsequently cared for an additional case in the same time interval with sudden death and similar pathological findings. No positive microbiological results were obtained, a negative finding possibly related to a 5-day antibiotics regimen. This report describes the pathological features of these cases and stresses the need to recognize PVL-positive S. aureus infections in young children. Finally, we believe that all lethal infections due to PVL-positive S. aureus, independently of the methicillin resistance profile, deserve a mandatory report to the provincial public health authorities.

Detection of Epstein-Barr virus in leucoreduced blood products.

This study examined the prevalence of three human herpesviruses (HHV), namely HHV‐4 (Epstein–Barr virus/EBV), HHV‐6b and HHV‐7 in leucoreduced blood products obtained from the Sainte‐Justine Hospital blood bank. A total of 100 specimens, including 34 red blood cell concentrates, 33 platelet bags and 33 plasma units, were collected and screened by a sensitive PCR assay using virus‐specific primers. Positive units were then retested by quantitative PCR. Of the 100 specimens, one platelet unit tested positive for EBV.

Hepatitis E virus seroprevalence before hematopoietic SCT: a pediatric experience

In a recent paper, Versluis et al. reported on hepatitis E virus (HEV) hepatitis as an emerging infectious diseases in adult recipients of hematopoietic SCT (HSCT). Recently, we reported on chronic HEV hepatitis in children, both in liver transplantation and in a HSCT recipient. The HSCT child ultimately died from hepatic complications. We concur with Versluis et al. that HEV is an underestimated and under recognized etiology for chronic hepatitis in the immunocompromised patient. The lack of data on HEV seroprevalence, especially in children, and our recent cases of HEV infection prompted us to estimate the seroprevalence of this virus in a pediatric population awaiting HSCT. We recruited children who had undergone HSCT for underlying hematological malignancies or primary immunodeficiency. Inclusion criteria were: age between 1 month and 19 years, and presenting with elevated serum aminotransferase values after HSCT (ALT ⩾ 60 IU/L; AST ⩾ 100 IU/L). As a control group, children without liver or chronic diseases were recruited from the Infectious Disease outpatient clinic and the home intravenous antibiotic program. Samples were tested for anti-HEV IgG and antiHEV IgM reactivity as previously described. We found an overall HEV IgG seroprevalence of 13.3% in our pediatric cohort of HSCT patients (Table 1). Of 75 patients undergoing allogeneic HSCT between January 2008 and December 2010, 63 had elevated aminotransferases and of those, 45 had available sera for serological tests. Six patients tested positive for anti-HEV IgG. The median age of HEV positive children was 7 years and 2 patients were younger than 1 year of age. All seropositive patients were born in Canada. Four of them lived in rural and two in urban areas. In the control group, HEV IgG seroprevalence was 6.9%. All sera were found to be negative for anti-HEV IgM in both groups. The seroprevalence in our control population is higher than the 3% IgG seropositivity previously described in a Canadian study. Most children in our control group lived in urban areas with high cultural diversity, a factor that may have influenced the seroprevalence. In our HSCT pediatric population, the seroprevalence is similar to that described in a German cohort of immunocompromised adults and by Versluis et al. The high HEV seroprevalence observed in our HSCT population could be explained by the selection criteria, which included only patients with elevated serum aminotransferases levels. It could also stem from the transfusion of blood products or the transfer of maternal antibodies in younger patients (⩽1-year-old). In conclusion, the high seroprevalence found by Versluis et al. and confirmed in our subgroup of HSCT children suggests that HEV infection is a more common opportunistic infection than previously suggested, both in children and adults. Altogether, these studies strengthen the indication for anti-HEV screening before transplant, especially in cases where peri-transplant transmission is highly suspected. Moreover, they suggest that HEV infection should be considered as an etiology of liver dysfunction in immunocompromised children.