Pylephlebitis combined with septic shock secondary to acute nonperforated appendicitis: a case report.

Pylephlebitis, which is a type of septic thrombophlebitis of the portal vein, is a rare and life-threatening complication that commonly occurs following appendicitis. However, nonspecific abdominal complaints and fever can impede the diagnosis of pylephlebitis. Timely use of appropriate antibiotics and anticoagulants is paramount for treating this condition. We present a case of pylephlebitis and septic shock caused by acute nonperforated appendicitis. A 32-year-old man presented with migratory right lower abdominal pain. Blood cultures showed the presence of Escherichia coli. Blood test results showed increased bilirubin concentrations and coagulation factor abnormalities. A computed tomographic abdominal scan showed that the portal vein had a widened intrinsic diameter. After intensive care treatment with antibiotics, antishock therapy, anticoagulants, and other supportive treatments, the infection was monitored, the abdominal pain disappeared, and the jaundice subsided. Laparoscopic appendectomy was performed. Histopathology showed acute suppurative appendicitis, and no abnormalities were observed during the follow-up period after discharge. A multidisciplinary approach is mandatory for the decision-making process in the presence of pylephlebitis caused by appendicitis to obtain a correct diagnosis and prompt treatment. Similarly, the timing of appendectomy is important for minimizing intra- and postoperative complications.

Comparison of bacteremic pneumonia caused by Escherichia coli and Klebsiella pneumoniae: A retrospective study.

OBJECTIVES: To compare the prognosis of bacteremic pneumonia caused by Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E. coli) pathogens. METHODS: A retrospective analysis was carried out on the clinical data of 162 patients who were diagnosed with bacterial pneumonia caused by either K. pneumoniae or E. coli between 2016-2019. The primary outcome of the analysis was the patients' 30-day mortality rate. RESULTS: There were 82 patients in the E. coli bacteremic pneumonia (E. coli-BP) group and 80 patients in the K. pneumoniae bacteremic pneumonia (KP-BP) group. The 30-day mortality rate was 43.75% (n=35/80) in the KP-BP group and 21.95% (n=18/82) in the E. coli-BP group (p<0.001). Following the adjustment for confounding variables in 4 distinct models, the hazard ratios for the primary outcome in KP-BP were determined to be 0.70 (95% confidence interval [CI]: [0.44-1.02]) in Model 1, 0.72 (95% CI: [0.46-1.14]) in Model 2, 0.99 (95% CI: [0.57-1.73]) in Model 3, and 1.22 (95% CI: [0.69-2.18]) in Model 4. CONCLUSION: Patients diagnosed with KP-BP exhibited a similar prognosis as those diagnosed with E. coli-BP. For patients with KP-BP, the risk of mortality was significantly higher for those who were in the intensive care unit, were infected with carbapenem-resistant strains, or had a high sequential organ failure assessment score. In patients with E. coli-BP, the Pitt bacteremia score was strongly associated with the 30-day mortality rate.

STEC colitis mimicking acute severe colitis with life-threatening consequences: a case report.

Acute colitis is a common feature of infection with Shiga-toxin producing Escherichia coli (STEC) and can mimic acute severe ulcerative colitis. Early recognition is important as there is a risk of developing Shiga toxin-induced haemolytic uremic syndrome (STEC-HUS), defined by the triad of microangiopathic haemolytic anemia, thrombocytopenia and organ damage. In severe cases STEC-HUS can cause severe neurological complications and can be fatal. We present a patient with a medical history of refractory ulcerative colitis, where making the diagnosis of STEC-HUS was challenging since the initial clinical presentation was difficult to differentiate from a flare of ulcerative colitis. This case illustrates that STEC induced colitis can mimic acute severe ulcerative colitis. This finding is of utmost clinical importance because of the potential life-threatening complications of STEC-HUS. Therefore it should be excluded promptly in patients with acute severe ulcerative colitis by using multiplex-PCR assay on a faecal sample.

The H9N2 avian influenza virus increases APEC adhesion to oviduct epithelia by viral NS1 protein-mediated activation of the TGF-ß pathway.

H9N2 avian influenza is a low-pathogenic avian influenza circulating in poultry and wild birds worldwide and frequently contributes to chicken salpingitis that is caused by avian pathogenic Escherichia coli (APEC), leading to huge economic losses and risks for food safety. Currently, how the H9N2 virus contributes to APEC infection and facilitates salpingitis remains elusive. In this study, in vitro chicken oviduct epithelial cell (COEC) model and in vivo studies were performed to investigate the role of H9N2 viruses on secondary APEC infection, and we identified that H9N2 virus enhances APEC infection both in vitro and in vivo. To understand the mechanisms behind this phenomenon, adhesive molecules on the cell surface facilitating APEC adhesion were checked, and we found that H9N2 virus could upregulate the expression of fibronectin, which promotes APEC adhesion onto COECs. We further investigated how fibronectin expression is regulated by H9N2 virus infection and revealed that transforming growth factor beta (TGF-ß) signaling pathway is activated by the NS1 protein of the virus, thus regulating the expression of adhesive molecules. These new findings revealed the role of H9N2 virus in salpingitis co-infected with APEC and discovered the molecular mechanisms by which the H9N2 virus facilitates APEC infection, offering new insights to the etiology of salpingitis with viral-bacterial co-infections.IMPORTANCEH9N2 avian influenza virus (AIV) widely infects poultry and is sporadically reported in human infections. The infection in birds frequently causes secondary bacterial infections, resulting in severe symptoms like pneumonia and salpingitis. Currently, the mechanism that influenza A virus contributes to secondary bacterial infection remains elusive. Here we discovered that H9N2 virus infection promotes APEC infection and further explored the underlying molecular mechanisms. We found that fibronectin protein on the cell surface is vital for APEC adhesion and also showed that H9N2 viral protein NS1 increased the expression of fibronectin by activating the TGF-ß signaling pathway. Our findings offer new information on how AIV infection promotes APEC secondary infection, providing potential targets for mitigating severe APEC infections induced by H9N2 avian influenza, and also give new insights on the mechanisms on how viruses promote secondary bacterial infections in animal and human diseases.

Gastrointestinal involvement in STEC-associated hemolytic uremic syndrome: 10 years in a pediatric center.

BACKGROUND: The gastrointestinal (GI) tract represents one of the main targets of typical hemolytic uremic syndrome (HUS) in children. In this observational study, we tried to establish (1) the main features of GI complications during STEC-HUS and (2) the relationship between Escherichia coli serotypes and Shiga toxin (Stx) variants with hepatopancreatic involvement. METHODS: A total of 79 STEC-HUS patients were admitted to our pediatric nephrology department between January 2012 and June 2021. Evidence of intestinal, hepatobiliary, and pancreatic involvements was reported for each patient, alongside demographic, clinical, and laboratory features. Frequency of gastrointestinal complications across groups of patients infected by specific E. coli serotypes and Stx gene variants was evaluated. RESULTS: Six patients developed a bowel complication: two developed rectal prolapse, and four developed bowel perforation which resulted in death for three of them and in bowel stenosis in one patient. Acute pancreatitis was diagnosed in 13 patients. An isolated increase in pancreatic enzymes and/or liver transaminases was observed in 41 and 15 patients, respectively. Biliary sludge was detected in three, cholelithiasis in one. Forty-seven patients developed direct hyperbilirubinemia. Neither E. coli serotypes nor Shiga toxin variants correlated with hepatic or pancreatic involvement. CONCLUSIONS: During STEC-HUS, GI complications are common, ranging from self-limited elevation of laboratory markers to bowel perforation, a severe complication with a relevant impact on morbidity and mortality. Hepatopancreatic involvement is frequent, but usually short-lasting and self-limiting.

Volume expansion mitigates Shiga toxin-producing E. coli-hemolytic uremic syndrome in children.

BACKGROUND: Shiga toxin-producing E. coli-hemolytic uremic syndrome (STEC-HUS) is associated with high morbidity and relevant mortality. Previous small studies showed that volume expansion could improve the course and outcome of STEC-HUS. The aim of this single-center study was to evaluate the effect of volume expansion on the clinical course and outcome in STEC-HUS. METHODS: Data of pediatric patients with STEC-HUS were analyzed retrospectively. Course and outcome of patients treated with volume expansion (VE) from 2019 to 2022 (n = 38) were compared to historical controls (HC) from 2009 to 2018 (n = 111). RESULTS: Patients in the VE group had a significant relative median weight gain compared to HC (7.8% (3.4-11.3) vs. 1.2% (- 0.7-3.9), p < 0.0001) 48 h after admission. The need for dialysis was not reduced by VE (VE 21/38 (55.3%) vs. HC 64/111 (57.7%), p = 0.8). However, central nervous system involvement (impairment of consciousness, seizures, focal neurological deficits, and/or visual disturbances) was significantly reduced (VE 6/38 (15.8%) vs. HC 38/111 (34.2%), p = 0.039). None of the patients in the VE group died or developed chronic kidney disease (CKD) stage 5, whereas in the HC group, three patients died and three patients had CKD stage 5 at discharge. CONCLUSIONS: This study suggests that volume expansion may be associated with the mitigation of the acute course of STEC-HUS, especially severe neurological involvement and the development of CKD. Prospective trials should lead to standardized protocols for volume expansion in children with STEC-HUS.

Red blood cell-derived arginase release in hemolytic uremic syndrome.

BACKGROUND: Hemolysis is a cardinal feature of hemolytic uremic syndrome (HUS) and during hemolysis excess arginase 1 is released from red blood cells. Increased arginase activity leads to reduced L-arginine, as it is converted to urea and L-ornithine, and thereby reduced nitric oxide bioavailability, with secondary vascular injury. The objective of this study was to investigate arginase release in HUS patients and laboratory models and correlate arginase levels to hemolysis and kidney injury. METHODS: Two separate cohorts of patients (n = 47 in total) with HUS associated with Shiga toxin-producing enterohemorrhagic E. coli (EHEC) and pediatric controls (n = 35) were investigated. Two mouse models were used, in which mice were either challenged intragastrically with E. coli O157:H7 or injected intraperitoneally with Shiga toxin 2. An in vitro model of thrombotic microangiopathy was developed in which Shiga toxin 2- and E. coli O157 lipopolysaccharide-stimulated human blood cells combined with ADAMTS13-deficient plasma were perfused over glomerular endothelial cells. Two group statistical comparisons were performed using the Mann-Whitney test, multiple groups were compared using the Kruskal-Wallis test followed by Dunn's procedure, the Wilcoxon signed rank test was used for paired data, or linear regression for continuous variables. RESULTS: HUS patients had excessively high plasma arginase 1 levels and activity (conversion of L-arginine to urea and L-ornithine) during the acute phase, compared to remission and controls. Arginase 1 levels correlated with lactate dehydrogenase activity, indicating hemolysis, as well as the need for dialysis treatment. Patients also exhibited high levels of plasma alpha-1-microglobulin, a heme scavenger. Both mouse models exhibited significantly elevated plasma arginase 1 levels and activity. Plasma arginase 1 levels correlated with lactate dehydrogenase activity, alpha-1-microglobulin and urea levels, the latter indicative of kidney dysfunction. In the in vitro model of thrombotic microangiopathy, bioactive arginase 1 was released and levels correlated to the degree of hemolysis. CONCLUSIONS: Elevated red blood cell-derived arginase was demonstrated in HUS patients and in relevant in vivo and in vitro models. The excessively high arginase levels correlated to the degree of hemolysis and kidney dysfunction. Thus, arginase inhibition should be investigated in HUS.

Eculizumab in severe Shiga toxin-mediated haemolytic uraemic syndrome.

Shiga toxin (Stx)-producing Escherichia coli-mediated haemolytic uraemic syndrome is a primary thrombotic microangiopathy, typified by the development of microangiopathic haemolytic anaemia, thrombocytopaenia and acute renal failure. It is a leading cause of acute renal failure in paediatrics, with a second peak in prevalence in adults over the age of 60. Presentations of Stx-producing E. coli-mediated haemolytic uraemic syndrome in young adults are rare. We present the case of a previously well female in her early 30s presenting with Stx-producing E. coli-mediated haemolytic uraemic syndrome with severe renal and neurological manifestations. Eculizumab was administered due to the severity of presentation and disease trajectory refractory to initial supportive therapy. A significant clinical and biochemical improvement was observed following eculizumab.

Acute pyelonephritis in cats is frequently caused by Escherichia coli resistant to potentiated penicillins but has a better prognosis than other causes of acute kidney injury.

OBJECTIVE: To describe the clinical findings, microbiological data, treatment, and outcome of a population of cats with suspected acute pyelonephritis (APN). ANIMALS: 32 client-owned cats. CLINICAL PRESENTATION AND PROCEDURES: Retrospective case series from 2 veterinary teaching hospitals between January 1, 2014, and December 31, 2020. Cats were included if they had a positive bacterial urine culture and a clinical diagnosis of acute kidney injury. RESULTS: Older female cats with underlying chronic kidney disease have a higher probability to develop bacterial culture-positive acute kidney injury or APN. Escherichia coli was the most commonly cultured bacterial species, and E coli isolates with susceptibility testing were resistant to amoxicillin-clavulanate but susceptible to fluoroquinolones or third-generation cephalosporins. Of the 20 cats with available follow-up information in the medical record, 14 were alive at 3 months after hospital discharge. Markers of renal function including creatinine (P = .008), BUN (P = .005), and phosphorus (P < .001) at the time of presentation were all higher in nonsurvivors compared with survivors. CLINICAL RELEVANCE: The survival rate with feline APN is higher than previous reports of acute kidney injury when all etiologies are considered. Nonsurvivors had more pronounced azotemia upon initial presentation. Amoxicillin-clavulanate was a poor empirical antimicrobial in this cohort based on the microbiological data.

Kidney sequelae in 281 Shiga toxin-producing Escherichia coli-hemolytic uremic syndrome patients after a median follow-up of 12 years.

BACKGROUND: A substantial proportion of patients with Escherichia coli-hemolytic uremic syndrome (STEC-HUS) evolve to chronic kidney disease (CKD). The objectives of this study were to evaluate long-term kidney outcomes and to identify CKD predictors. METHODS: In this single-center retrospective study, long-term outcomes of patients were analyzed according to the presence of complete recovery (CR) or CKD at last visit. Then, they were grouped into favorable (CR + CKD1) or poor (CKD2-5) outcome to compare predictors at diagnosis (sex, age, leukocytes, creatinine, hemoglobin, HUS severity score), dialysis duration, and follow-up time between them. RESULTS: Of 281 patients followed up for a median of 12 years, 139 (49%) had CR, 104 (37%) CKD1, 27 (10%) CKD2-4, and 11 (4%) CKD5. Thirty-eight patients progressed to CKD2-5 after a median of 4.8 years, 7% in the first 5 years, increasing to 8%, 10%, and 14% after 5-10 years, 10-15 years, and > 15 years, respectively. They were younger, had higher baseline hemoglobin and leukocytes, and required longer dialysis and follow-up than those with favorable outcome. By multivariate analysis, days of dialysis and follow-up time remained as independent predictors of poor outcome. The best cutoff for days of dialysis was 10 days. After 5 years, 20% of those dialyzed ≥ 10 days evolved to CKD2-5 versus 1% of those non-dialyzed or dialyzed < 10 days. CONCLUSIONS: Fifty-one percent of patients evolved to CKD after 12 years of follow-up and 14% to CKD2-5. Ten days of dialysis was the best cutoff to recognize outcomes. In some cases, kidney damage was evident after 15 years of surveillance, highlighting the need for follow-up until adulthood in all STEC-HUS patients.

Constipation and hemolytic uremic syndrome.

BACKGROUND: Shiga toxin-producing Escherichia coli (STEC) hemolytic uremic syndrome (HUS) classically presents with diarrhea. Absence of diarrheal prodrome increases suspicion for atypical HUS (aHUS). Inability to obtain a fecal specimen for culture or culture-independent testing limits the ability to differentiate STEC-HUS and aHUS. CASE-DIAGNOSIS/TREATMENT: Our patient presented with abdominal pain and constipation, and evaluation of pallor led to a diagnosis of HUS. There was a complete absence of diarrhea during the disease course. Lack of fecal specimen for several days delayed testing for STEC. Treatment for atypical HUS was initiated with complement-blockade therapy. PCR-testing for Shiga toxin from fecal specimen later returned positive. Alternative complement-pathway testing did not identify a causative genetic variant or anti-Factor H antibody. A diagnosis of STEC-HUS was assigned, and complement-blockade therapy was stopped. CONCLUSION: Diagnosis of aHUS remains a diagnosis of exclusion, whereby other causes of HUS are eliminated with reasonable certainty. Exclusion of STEC is necessary and relies on testing availability and recognition of testing limitations. Diarrhea-negative STEC-HUS remains a minority of cases, and future research is needed to explore the clinical characteristics of these patients.

Shiga toxin targets the podocyte causing hemolytic uremic syndrome through endothelial complement activation.

BACKGROUND: Shiga toxin (Stx)-producing Escherichia coli hemolytic uremic syndrome (STEC-HUS) is the leading cause of acute kidney injury in children, with an associated mortality of up to 5%. The mechanisms underlying STEC-HUS and why the glomerular microvasculature is so susceptible to injury following systemic Stx infection are unclear. METHODS: Transgenic mice were engineered to express the Stx receptor (Gb3) exclusively in their kidney podocytes (Pod-Gb3) and challenged with systemic Stx. Human glomerular cell models and kidney biopsies from patients with STEC-HUS were also studied. FINDINGS: Stx-challenged Pod-Gb3 mice developed STEC-HUS. This was mediated by a reduction in podocyte vascular endothelial growth factor A (VEGF-A), which led to loss of glomerular endothelial cell (GEnC) glycocalyx, a reduction in GEnC inhibitory complement factor H binding, and local activation of the complement pathway. Early therapeutic inhibition of the terminal complement pathway with a C5 inhibitor rescued this podocyte-driven, Stx-induced HUS phenotype. CONCLUSIONS: This study potentially explains why systemic Stx exposure targets the glomerulus and supports the early use of terminal complement pathway inhibition in this devastating disease. FUNDING: This work was supported by the UK Medical Research Council (MRC) (grant nos. G0901987 and MR/K010492/1) and Kidney Research UK (grant nos. TF_007_20151127, RP42/2012, and SP/FSGS1/2013). The Mary Lyon Center is part of the MRC Harwell Institute and is funded by the MRC (A410).

Cardiovascular impairment in Shiga-toxin-2-induced experimental hemolytic-uremic syndrome: a pilot study.

Introduction: Hemolytic-uremic syndrome (HUS) can occur as a systemic complication of infection with Shiga toxin (Stx)-producing Escherichia coli (STEC). Most well-known aspects of the pathophysiology are secondary to microthrombotic kidney disease including hemolytic anemia and thrombocytopenia. However, extrarenal manifestations, such as cardiac impairment, have also been reported. We have investigated whether these cardiac abnormalities can be reproduced in a murine animal model, in which administration of Stx, the main virulence factor of STEC, is used to induce HUS. Methods: Mice received either one high or multiple low doses of Stx to simulate the (clinically well-known) different disease courses. Cardiac function was evaluated by echocardiography and analyses of biomarkers in the plasma (troponin I and brain natriuretic peptide). Results: All Stx-challenged mice showed reduced cardiac output and depletion of intravascular volume indicated by a reduced end-diastolic volume and a higher hematocrit. Some mice exhibited myocardial injury (measured as increases in cTNI levels). A subset of mice challenged with either dosage regimen showed hyperkalemia with typical electrocardiographic abnormalities. Discussion: Myocardial injury, intravascular volume depletion, reduced cardiac output, and arrhythmias as a consequence of hyperkalemia may be prognosis-relevant disease manifestations of HUS, the significance of which should be further investigated in future preclinical and clinical studies.

An Intestinal Th17 Subset is Associated with Inflammation in Crohn's Disease and Activated by Adherent-invasive Escherichia coli.

IFNγ-producing ex-Th17 cells ['Th1/17'] were shown to play a key pathogenic role in experimental colitis and are abundant in the intestine. Here, we identified and characterised a novel, potentially colitogenic subset of Th17 cells in the intestine of patients with Crohn's disease [CD]. Human Th17 cells expressing CCR5 ['pTh17'] co-expressed T-bet and RORC/γt and produced very high levels of IL-17, together with IFN-γ. They had a gene signature of Th17 effector cells and were distinct from established Th1/17 cells. pTh17 cells, but not Th1/17 cells, were associated with intestinal inflammation in CD, and decreased upon successful anti-TNF therapy with infliximab. Conventional CCR5[-]Th17 cells differentiated to pTh17 cells with IL-23 in vitro. Moreover, anti-IL-23 therapy with risankizumab strongly reduced pTh17 cells in the intestine. Importantly, intestinal pTh17 cells were selectively activated by adherent-invasive Escherichia coli [AIEC], but not by a commensal/probiotic E. coli strain. AIEC induced high levels of IL-23 and RANTES from dendritic cells [DC]. Intestinal CCR5+Th1/17 cells responded instead to cytomegalovirus and were reduced in ulcerative colitis [UC], suggesting an unexpected protective role. In conclusion, we identified an IL-23-inducible subset of human intestinal Th17 cells. pTh17 cells produced high levels of pro-inflammatory cytokines, were selectively associated with intestinal inflammation in CD, and responded to CD-associated AIEC, suggesting a key colitogenic role.

Escherichia coli-associated follicular cystitis in dogs: Clinical and pathologic characterization.

BACKGROUND: Follicular cystitis is an uncommon inflammatory change in the urinary bladder wall characterized by the formation of tertiary lymphoid structures (TLSs) in the submucosa. OBJECTIVES: To characterize clinical and pathologic features of follicular cystitis in dogs and to explore in situ distribution and possible role of Escherichia coli as an associated cause. ANIMALS: Eight dogs diagnosed with follicular cystitis and 2 control dogs. METHODS: Retrospective descriptive study. Dogs diagnosed with follicular cystitis (macroscopic follicular lesions in the urinary bladder mucosa and histopathologic detection of TLSs in bladder wall biopsies) were identified from medical records. Paraffin embedded bladder wall biopsies were subject to in situ hybridization for E. coli 16SrRNA identification. RESULTS: Follicular cystitis was diagnosed in large breed (median weight 24.9 kg, interquartile range [IQR] 18.8-35.4 kg) female dogs with a history of chronic recurrent urinary tract infections (UTIs; median duration of clinical signs 7 months, IQR 3-17 months; median number of previous UTIs 5, IQR 4-6). Positive E. coli 16SrRNA signal was detected within developing, immature and mature TLSs in 7/8 dogs, through submucosal stroma in 8/8 dogs and within the urothelium in 3/8 dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Chronic inflammation associated with an intramural E. coli infection in the urinary bladder wall represents a possible triggering factor for the development of follicular cystitis.

Hyperhydration to Improve Kidney Outcomes in Children with Shiga Toxin-Producing E. coli Infection: a multinational embedded cluster crossover randomized trial (the HIKO STEC trial).

BACKGROUND: Shiga toxin-producing E. coli (STEC) infections affect children and adults worldwide, and treatment remain solely supportive. Up to 15-20% of children infected by high-risk STEC (i.e., E. coli that produce Shiga toxin 2) develop hemolytic anemia, thrombocytopenia, and kidney failure (i.e., hemolytic uremic syndrome (HUS)), over half of whom require acute dialysis and 3% die. Although no therapy is widely accepted as being able to prevent the development of HUS and its complications, several observational studies suggest that intravascular volume expansion (hyperhydration) may prevent end organ damage. A randomized trial is needed to confirm or refute this hypothesis. METHODS: We will conduct a pragmatic, embedded, cluster-randomized, crossover trial in 26 pediatric institutions to determine if hyperhydration, compared to conservative fluid management, improves outcomes in 1040 children with high-risk STEC infections. The primary outcome is major adverse kidney events within 30 days (MAKE30), a composite measure that includes death, initiation of new renal replacement therapy, or persistent kidney dysfunction. Secondary outcomes include life-threatening, extrarenal complications, and development of HUS. Pathway eligible children will be treated per institutional allocation to each pathway. In the hyperhydration pathway, all eligible children are hospitalized and administered 200% maintenance balanced crystalloid fluids up to targets of 10% weight gain and 20% reduction in hematocrit. Sites in the conservative fluid management pathway manage children as in- or outpatients, based on clinician preference, with the pathway focused on close laboratory monitoring, and maintenance of euvolemia. Based on historical data, we estimate that 10% of children in our conservative fluid management pathway will experience the primary outcome. With 26 clusters enrolling a mean of 40 patients each with an intraclass correlation coefficient of 0.11, we will have 90% power to detect a 5% absolute risk reduction. DISCUSSION: HUS is a devastating illness with no treatment options. This pragmatic study will determine if hyperhydration can reduce morbidity associated with HUS in children with high-risk STEC infection. TRIAL REGISTRATION: ClinicalTrials.gov NCT05219110 . Registered on February 1, 2022.

Site-Specific Analysis of the Incidence Rate of Enterotoxigenic Escherichia coli Infection Elucidates an Association with Childhood Stunting, Wasting, and Being Underweight: A Secondary Analysis of the MAL-ED Birth Cohort.

Asymptomatic infection by fecal enteropathogens is a major contributor to childhood malnutrition. Here, we investigated the incidence rate of asymptomatic infection by enterotoxigenic Escherichia coli (ETEC) and assessed its association with childhood stunting, wasting, and being underweight among children under 2 years of age. The Malnutrition and Enteric Disease birth cohort study included 1,715 children who were followed from birth to 24 months of age from eight distinct geographic locations including Bangladesh, Brazil, India, Peru, Tanzania, Pakistan, Nepal, and South Africa. The TaqMan array card assay was used to determine the presence of ETEC in the nondiarrheal stool samples collected from these children. Poisson regression was used to estimate the incidence rate, and multiple generalized estimating equations with binomial family, logit link function, and exchangeable correlation were used to analyze the association between asymptomatic ETEC infection and anthropometric indicators such as stunting, wasting, and being underweight. The site-specific incidence rates of asymptomatic ETEC infections per 100 child-months were also higher at the study locations in Tanzania (54.81 [95% CI: 52.64, 57.07]) and Bangladesh (46.75 [95% CI: 44.75, 48.83]). In the Bangladesh, India, and Tanzania sites, the composite indicator of anthropometric failure was significantly associated with asymptomatic ETEC infection. Furthermore, a significant association between asymptomatic heat-stable toxin ETEC infections and childhood stunting, wasting, and being underweight was found in only the Bangladesh and Tanzania sites.