Surveillance of Shiga toxin-producing Escherichia coli associated bloody diarrhea in Argentina / Vigilancia de diarrea sanguinolenta asociada a Escherichia coli productor de toxina Shiga en Argentina

Abstract In Argentina, hemolytic uremic syndrome (HUS) caused by Shiga toxin-producing Escherichia coli (STEC-HUS) infection is endemic, and reliable data about prevalence and risk factors have been available since 2000. However, information about STEC-associated bloody diarrhea (BD) is limited. A prospective study was performed during the period October Surveillance; 2018-June 2019 in seven tertiary-hospitals and 18 referral units from different regions, aiming of STEC-HUS cases in the same hospitals and during the same period were also assessed. Twenty-nine (4.1%) of the BD patients were STEC-positive, as determined by the Shiga Toxin Quik Chek (STQC) test and/or the multiplex polymerase chain reaction (mPCR) assay. The highest fre-quencies were found in the Southern region (Neuquén, 8.7%; Bahía Blanca, 7.9%), in children between 12 and 23 month of age (8.8%), during summertime. Four (13.8%) cases progressed to HUS, three to nine days after diarrhea onset. Twenty-seven STEC-HUS in children under 5 years of age (77.8%) were enrolled, 51.9% were female; 44% were Stx-positive by STQC and all by mPCR. The most common serotypes were O157:H7 and O145:H28 and the prevalent geno-types, both among BD and HUS cases, were sfx2a-only or -associated. Considering the endemic behavior of HUS and its high incidence, these data show that the rate of STEC-positive cases is low among BD patients. However, the early recognition of STEC-positive cases is important for patient monitoring and initiation of supportive treatment.

Resumen En Argentina, el síndrome urémico hemolítico asociado a Escherichia coli productor de toxina Shiga (STEC-SUH) es endémico y, desde 2000, de notificación obligatoria. Sin embargo, la información sobre diarrea sanguinolenta (DS) asociada a STEC (DS-STEC) es limitada. Se realizó un estudio prospectivo desde octubre de 2018 hasta junio de 2019 en siete hospitales de tercer nivel y 18 unidades de referencia de diferentes provincias argentinas, con el objetivo de determinar la frecuencia de casos de DS-STEC en 714 niños de 1 a 9 años que tuvieron DS (I) y la tasa de progresión de DS a SUH en dicha cohorte (II). También se evaluó el número y distribución regional de casos de STEC-SUH en los mismos hospitales en dicho período. Veintinueve casos de DS (4,1%) fueron STEC-positivos, determinados por Shiga Toxin Quik Chek (STQC) o PCR múltiple (mPCR). Las frecuencias más altas se encontraron en el sur del área relevada (Neuquén, 8,7%; Bahía Blanca, 7,9%), en niños de 12 a 23 meses (8,8%), en verano. Cuatro casos de DS-STEC (13,8%) progresaron a SUH, de tres a nueve días después del inicio de la diarrea. Se registraron 27 niños con STEC-SUH, estos fueron mayoritariamente <5 anos (77,8%) del sexo femenino (51,9%). El 44% de estos casos fueron Stx-positivos por STQC y todos por mPCR. Los serotipos más comunes fueron O157:H7y O145:H28, y el genotipo predominante fue stx2a, solo o asociado, en DS y SUH. Considerando el comportamiento endémico del SUH y su alta incidencia, estos datos muestran que la tasa de casos de DS-STEC es baja. Sin embargo, su reconocimiento temprano es importante para el seguimiento e inicio del tratamiento de sostén.

Surveillance of Shiga toxin-producing Escherichia coli associated bloody diarrhea in Argentina.

In Argentina, hemolytic uremic syndrome (HUS) caused by Shiga toxin-producing Escherichia coli (STEC-HUS) infection is endemic, and reliable data about prevalence and risk factors have been available since 2000. However, information about STEC-associated bloody diarrhea (BD) is limited. A prospective study was performed during the period October 2018-June 2019 in seven tertiary-hospitals and 18 referral units from different regions, aiming to determine (i) the frequency of STEC-positive BD cases in 714 children aged 1-9 years of age and (ii) the rate of progression of bloody diarrhea to HUS. The number and regional distribution of STEC-HUS cases in the same hospitals and during the same period were also assessed. Twenty-nine (4.1%) of the BD patients were STEC-positive, as determined by the Shiga Toxin Quik Chek (STQC) test and/or the multiplex polymerase chain reaction (mPCR) assay. The highest frequencies were found in the Southern region (Neuquén, 8.7%; Bahía Blanca, 7.9%), in children between 12 and 23 month of age (8.8%), during summertime. Four (13.8%) cases progressed to HUS, three to nine days after diarrhea onset. Twenty-seven STEC-HUS in children under 5 years of age (77.8%) were enrolled, 51.9% were female; 44% were Stx-positive by STQC and all by mPCR. The most common serotypes were O157:H7 and O145:H28 and the prevalent genotypes, both among BD and HUS cases, were stx2a-only or -associated. Considering the endemic behavior of HUS and its high incidence, these data show that the rate of STEC-positive cases is low among BD patients. However, the early recognition of STEC-positive cases is important for patient monitoring and initiation of supportive treatment.

Influence of CYP3A5 polymorphism on tacrolimus maintenance doses and serum levels after renal transplantation: age dependency and pharmacological interaction with steroids.

TAC, MMF and MP are used in pediatric kidney tx. The cytochrome P450 (CYP)3A5 enzyme appears to play a role in TAC metabolism. The aims of this study were to investigate CYP3A5 polymorphism's effect on TAC dosing and the age dependency of TAC dosing by testing blood concentrations, and the interaction between steroids and TAC during the first year after tx. Genomic DNA was extracted and amplified with specific primers. CYP3A5 alleles were confirmed by direct sequencing of PCR products on an automated AB13100 capillary sequencer. We studied 48 renal transplant patients (age at tx 12±0.5yr, 22 boys) receiving TAC, MMF, MP. Of these, 79% were CYP3A5*3/*3 (non-expressers homozygotes) and 21% were CYP3A5*1/*3 (expressers). TAC trough levels were 7.1±0.4ng/mL in CYP3A5*3/*3 patients and 6.5±0.7ng/mL in CYP3A5*1/*3 group (p=0.03). CYP3A5*1/*3 patients had lower levels of dose-adjusted TAC (36.7±5.8ng/mL/mg/kg/day) to achieve target blood concentration and required higher daily dose per weight (0.21±0.03mg/kg/day) than CYP3A5*3/*3 patients, 72.4±8.0ng/mL/mg/kg/day and 0.13±0.01mg/kg/day (p<0.001). Prepubertal patients with different CYP3A5 polymorphisms required significant higher TAC doses and achieved lower dose-normalized concentration compared with pubertal patients. Both TAC dose and adjusted-dose correlated with daily MP dose in CYP3A5*1*3 (r: 0.4, p<0.03 and r: 0.4, p<0.03) and in CYP3A5*3*3 (r: 0.6, p<0.01 and r: 0.47, p<0.001) patients. CYP3A5 polymorphism performed before tx could contribute to a better individualization of TAC therapy. The higher TAC dose in prepubertal patients and the pharmacological interactions between MP and TAC may not be fully explained by different CYP3A5 polymorphisms.

Improved long-term allograft function in pediatric renal transplantation with mycophenolate mofetil.

MMF has been shown to decrease the incidence of acute rejection in children and adults at 1 and 3 yr. Other beneficial effects of MMF have been more difficult to demonstrate. Our open-labeled study presents a 5-yr data for patients and graft survival, allograft function, and growth in MMF-treated patients. The trial included 29 patients who were treated with MMF in combination with cyclosporine and methylprednisone. Patients were compared with a preceding group of 29 patients treated with AZA instead of MMF. Patient and graft survival rate 5 yr after transplantation were 97 and 90% in the MMF group vs. 93 and 83% in the AZA group (p: NS). Acute rejection was 20.6% in the MMF group vs. 58.6% in the AZA group (p < 0.01). Chronic rejection was 10.3% in the MMF group and 25% in the AZA group (p: NS). The changes in the creatinine clearance from baseline to 5 yr (Delta) were different between groups (-6.0 +/- 5.1 mL/min/1.73 m(2) in the MMF group vs. -22.2 +/- 7.6 mL/min/1.73 m(2) in the AZA group, p < 0.05). Also, the slope of 1/Scr showed a significant lower incidence of worsening renal function after the second year of renal transplantation (p < 0.0001) in the MMF group compared with the AZA group. Delta Height SDS in prepubertal patients was 0.3 +/- 0.4 SDS in the MMF group vs. -0.8 +/- 0.2 SDS in the AZA group (p < 0.05). This study shows that long-term MMF therapy has resulted in a decrease in acute rejection and was associated with a protection against renal function deterioration. The use of MMF enables a reduction in the dose of steroids and leads to a linear growth improvement of children after renal transplantation.