Implementation of multiplex PCR diagnostics for gastrointestinal pathogens linked to increase of notified Shiga toxin-producing Escherichia coli cases in Norway, 2007-2017.

The aim of this study was to investigate implementation of multiplex PCR assays (broad screening PCR) on the distribution and characteristics of notified Shiga toxin-producing Escherichia coli (STEC) cases in Norway, 2007-2017. We described STEC cases notified to the Norwegian Surveillance System for Communicable Diseases (MSIS), 2007-2017 and categorised cases as high-virulent, low-virulent or unclassifiable STEC infections based on guidelines for follow-up of STEC cases. We conducted descriptive analysis and time series analysis allowing for trends and seasonality, and calculated adjusted incidence rate ratios (aIRR) using negative binomial regression for laboratories with and without broad screening PCR. A total of 1458 STEC cases were notified to MSIS (2007-2017), median age 21 years, 51% female. Cases were categorised as having 475 (33%) high-virulent, 652 (45%) low-virulent, and 331 (23%) unclassifiable STEC infections. We observed a higher increasing monthly trend in cases (aIRR = 1.020; 95% CI 1.016-1.024) notified from laboratories with broad screening PCR (n = 4) compared to laboratories (n = 17) without (aIRR = 1.011; 95% CI 1.007-1.014). Notification of low-virulent STEC infections increased from laboratories with broad screening PCR. The increase in notified STEC cases was prominent in cases categorised with a low-virulent STEC infection and largely attributable to unselective screening methods. We recommend NIPH to maintain differentiated control measures for STEC cases to avoid follow-up of low-virulent STEC infections. We recommend microbiological laboratories in Norway to consider a more cost-effective broad screening PCR strategy that enables differentiation of high-virulent STEC infections.

Clinical features, therapeutic interventions and long-term aspects of hemolytic-uremic syndrome in Norwegian children: a nationwide retrospective study from 1999-2008.

BACKGROUND: Hemolytic-uremic syndrome (HUS) is a clinical triad of microangiopathic hemolytic anemia, impaired renal function and thrombocytopenia, primarily affecting pre-school-aged children. HUS can be classified into diarrhea-associated HUS (D(+)HUS), usually caused by Shiga toxin-producing Escherichia coli (STEC), and non-diarrhea-associated HUS (D(-)HUS), both with potentially serious acute and long-term complications. Few data exists on the clinical features and long-term outcome of HUS in Norway. The aim of this paper was to describe these aspects of HUS in children over a 10-year period. METHODS: We retrospectively collected data on clinical features, therapeutic interventions and long-term aspects directly from medical records of all identified HUS cases <16 years of age admitted to Norwegian pediatric departments from 1999 to 2008. Cases of D(+)HUS and D(-)HUS are described separately, but no comparative analyses were possible due to small numbers. Descriptive statistics are presented in proportions and median values with ranges, and/or summarized in text. RESULTS: Forty seven HUS cases were identified; 38 D(+)HUS and nine D(-)HUS. Renal complications were common; in the D(+)HUS and D(-)HUS group, 29/38 and 5/9 developed oligoanuria, 22/38 and 3/9 needed dialysis, with hemodialysis used most often in both groups, and plasma infusion(s) were utilized in 6/38 and 4/9 patients, respectively. Of extra-renal complications, neurological complications occurred in 9/38 and 2/9, serious gastrointestinal complications in 6/38 and 1/9, respiratory complications in 10/38 and 2/9, and sepsis in 11/38 and 3/9 cases, respectively. Cardiac complications were seen in two D(+)HUS cases. In patients where data on follow up ≥1 year after admittance were available, 8/21 and 4/7 had persistent proteinuria and 5/19 and 4/5 had persistent hypertension in the D(+)HUS and D(-)HUS group, respectively. Two D(+)HUS and one D(-)HUS patient were diagnosed with chronic kidney disease and one D(+)HUS patient required a renal transplantation. Two D(+)HUS patients died in the acute phase (death rate; 5 %). CONCLUSIONS: The HUS cases had a high rate of complications and sequelae, including renal, CNS-related, cardiac, respiratory, serious gastrointestinal complications and sepsis, consistent with other studies. This underlines the importance of attention to extra-renal manifestations in the acute phase and in renal long-term follow-up of HUS patients.

The incidence and aetiology of acute kidney injury in children in Norway between 1999 and 2008.

AIM: Primary acute kidney injury (AKI) is a direct cause of hospitalisation in children, but can also result from other conditions. There is limited information on the epidemiology of this condition. Our aim was to describe the national incidence rate and aetiology of acute kidney injury in children under the age of 16 in Norway from 1999 to 2008. METHODS: We carried out a retrospective study of medical records provided by all 18 of the paediatric hospital departments that specialise in treating paediatric patients with AKI. RESULTS: We identified 315 cases of AKI (53% male), with an estimated average annual incidence rate of 3.3 cases per 100 000 children and a median annual occurrence of 33 cases. Most cases (43%) were in children under five. We identified 53 aetiologies and classified these into 30 aetiological groups: 24% of the cases were prerenal (n = 75), 74% were intrinsic/renal (n = 234) and 2% were postrenal (n = 5). Nephritic syndromes was the major cause (44%) of AKI, followed by haemolytic-uraemic syndrome (HUS) (15%). CONCLUSION: Nephritic syndromes and HUS are the most common aetiologies of AKI in Norway. Although our results could indicate a low incidence of paediatric AKI in Norway, the lack of other national studies makes comparisons difficult.

Incidence and etiology of hemolytic-uremic syndrome in children in Norway, 1999-2008--a retrospective study of hospital records to assess the sensitivity of surveillance.

BACKGROUND: Public awareness of hemolytic-uremic syndrome (HUS), especially related to Shiga toxin-producing Escherichia coli (STEC), has increased in Europe in recent years; accentuated in Norway by a national outbreak in 2006 and in a European context especially by the 2011 outbreak originating in Germany. As STEC surveillance is difficult due to diagnostic challenges in detecting non-O157 infections, surveillance of HUS can be used to indicate the burden of STEC infection. Until 2006, notification of HUS to the Norwegian Communicable Disease Surveillance System (MSIS) was based on microbiologically confirmed infection with enterohemorrhagic Escherichia coli (EHEC), humanpathogenic STEC. In 2006, diarrhea-associated HUS (D(+)HUS) was made notifiable based on clinical criteria alone. The incidence and etiology of HUS in children in Norway has not previously been described. METHODS: In order to assess the sensitivity of STEC and D+HUS surveillance and describe the incidence and etiology of HUS in children in Norway, we conducted a nationwide retrospective study collecting data from medical records from pediatric departments for the period 1999-2008 and compared them with data from MSIS. Descriptive statistics are presented as proportions, median, average and mean values with ranges and as incidence rates, calculated using population numbers provided by official registries. RESULTS: Forty-seven HUS cases were identified, corresponding to an average annual incidence rate of 0.5 cases per 100,000 children. Diarrhea-associated HUS was identified in 38 (81%) cases, of which the median age was 29 months, 79% were <5 years of age and 68% were girls. From 1999 to 2006, thirteen more diarrhea-associated HUS cases were identified than had been notified to MSIS. From the change in notification criteria to 2008, those identified corresponded to those notified. STEC infection was verified in 23 (49%) of the HUS cases, in which O157 was the most frequently isolated sporadic serogroup. CONCLUSIONS: Our results show that the incidence of HUS in children in Norway is low and suggest that D+HUS cases may be underreported when notification requires microbiological confirmation. This may also indicate underreporting of STEC infections.