Haemolytic anaemia in association withEscherichia coli 0157 infection in two sisters

Two sisters, 2 and 5 years of age, suffered from acute haemolytic anaemia occurring after gastroenteritis withEscherichia coli 0157. One patient developed clinical signs of severe and acute intravascular haemolytis and sepsis. She received transfusion and antibiotic therapy. The second patient presented with mild to moderate haemolytic symptoms only. None of them developed renal impairment. In serum of both children, elevated titres of short-lived agglutinins were demonstrated in the indirect haemagglutination assay consisting of sheep erythrocytes coated with lipopolysaccharide fromE. coli 0157. By immunoblot analysis IgM antibodies against the 0157 lipopolysaccharide were demonstrated in the acute phase sera but not in follow up sera taken 2 months after disease. On erythrocyte membranes, adsorption of microbial antigens was detected by use of a pool-immunoglobulin fluorescence test. The immunological status of both patients was normal. Complete recovery from haemolytic disease was observed without further therapy. Microbial antigens attached to the cell surface were assumed to be the pathophysiological cause ofE. coli 0157 associated haemolytic anaemia in two siblings.     

Verocytotoxin-producingEscherichia coli infection in hemolytic uremic syndrome in part of Western Europe

From September 1989 until September 1993, stool specimens and sera from 113 children with diarrhoea-associated haemolytic uraemic syndrome (HUS) from the Netherlands, two university hospitals in Belgium and one university hospital in Germany were examined for the presence of verocytotoxin-producingEscherichia coli (VTEC) infection. Evidence for VTEC infection was observed in 88 (78%) patients with HUS compared to 2 (3%) of the 65 children with acute gastro-enteritis Serotype O157 was the causative agent in 76 (86%) of these 88 patients with VTEC-associated HUS and verocytotoxin-2 (VT-2) was the most frequent toxin produced. Serological testing for antibodies to O157 O-antigen yielded the highest number of positive results compared to the other test methods. Antibodies to O157 were found in sera of 71 (65%) of 110 patients with HUS and one control serum. Stool and sera examination for VTEC in 95 family contacts of 28 patients with HUS demonstrated an evidence for VTEC infection 33 (35%). In contrast, in patients with HUS serological antibodies to O157 O-antigen were found in only 3 (4%) of 85 family contacts.     

A severe outbreak of haemorrhagic colitis and haemolytic uraemic syndrome associated withEscherichia coli 0157: H7 in Japan

In 1990, an outbreak ofEscherichia coli 0157: H7 infection occurred in 174 children in a nursery school in Saitama, Japan. The organism was isolated from tap water supplied from the well in the school. Clinical manifestations varied from asymptomatic infection to non-bloody diarrhoea, haemorrhagic colitis, haemolytic uraemic syndrome (HUS) and death. Among culture-confirmed 42 cases ofE. coli 0157: H7, 7 children were asymptomatic, 21 children had only diarrhoea, and 14 children developed HUS. Bloody diarrhoea with abdominal pain following initial frequent diarrhoea appeared to be associated with subsequent HUS. In patients with HUS, both leucocyte count and lactate dehydrogenase activity continued to increase in the early phase of the disease, and on day 3 of illness attained markedly higher levels than in patients without HUS. These two parameters seemed to be important as predictors of the development of HUS.Committee for epidemiological and clinical study of epidemic diarrhoea due to pathogenicE. coli in a nursery school, Saitama, Japan     

Prolonged anemia by superinfection of parvovirus B19 in a boy with enterohemorrhagic <Emphasis Type="Italic">Escherichia coli</Emphasis> O157-associated hemolytic uremic syndrome

We report a 3-year-old boy with enterohemorrhagic Escherichia coli (EHEC) O157-associated hemolytic uremic syndrome (HUS). His anemia was associated with decreased reticulocyte count and persisted after the recovery from HUS. Superinfection of parvovirus B19 (PVB19) was proven by a transient febrile episode associated with IgM antibodies to the virus and the delayed appearance of IgG antibodies and typical rashes. We conclude that PVB19 infection could induce severe persistent anemia in EHEC-associated HUS. Reticulocytopenia is a clue to the diagnosis in such cases.     

Colostrum from healthy Brazilian women inhibits adhesion and contains IgA antibodies reactive with Shiga toxin-producing <Emphasis Type="Italic"> Escherichia coli</Emphasis>

Although Shiga toxin-producing Escherichia coli (STEC) has been isolated in Brazil, severe manifestations of the infection, such as haemorrhagic colitis and haemolytic-uraemic syndrome, are extremely rare in our population. Enteropathogenic Escherichia coli (EPEC) is the main aetiological agent of acute infantile diarrhoea in Brazil. There are many similarities between STEC and EPEC, such as the ability to produce attaching and effacing (A/E) lesions and some virulence-associated factors. Our aim was to investigate the presence of anti-STEC antibodies in healthy people living in an EPEC endemic area. Colostrum samples collected from 51 women living in low socio-economic conditions were analysed. Two STEC strains: O111:H- (Stx1) and O157:H7 (Stx2), and one EPEC strain (O111:H-) were used in the bacterial adhesion assays to HEp-2 cells, in the Stx1 and Stx2 cytotoxicity assays on Vero cells, in immunoblotting and in ELISA assays. All the samples strongly inhibited the adhesion of the three strains and contained SIgA antibodies reactive with antigens of EPEC O111:H-, STEC O111:H- and STEC O157:H7, mainly STEC and EPEC 94 kDa adhesin intimin. High titres of anti-LPS O111 antibodies were found in many samples. Nevertheless, the cytotoxic effect of both Stx1 and Stx2 on Vero cells was not neutralised by any sample. Conclusion: Our results suggest that Brazilian people may be exposed to Shiga toxin-producing Escherichia coli more frequently than previously thought or alternatively there may be a cross reactive immunity between enteropathogenic Escherichia coli and Shiga toxin-producing Escherichia coli.     

Haemolytic uraemic syndrome and pulmonary hypertension in a patient with methionine synthase deficiency

An 18-month-old girl presented with macrocytic megaloblastic anaemia followed by haemolytic uraemic syndrome. Metabolic investigations led to the identification of an inborn error of cobalamin metabolism consisting of defective methylcobalamin biosynthesis, probably cobalamin G, since methionine synthase activity was decreased under standard reducing conditions. Despite treatment, pulmonary hypertension progressively developed and responded to oxygen therapy. Renal involvement evolved to terminal failure and haemodialysis, while pulmonary hypertension was controlled by oxygen therapy. Such clinical manifestations have never been reported in association with a defect of methylcobalamin and thus of methionine biosynthesis. Conclusion A congenital abnormality of cobalamin metabolism was suspected then confirmed in the presence of typical haematological features associated with unusual clinical manifestations such as progressive renal failure and pulmonary hypertension. Received: 12 June 1998 and in revised form: 13 October 1998 and 21 December 1998 / Accepted: 10 January 1999     

Colonic complications of the haemolytic-uraemic syndrome

Ischaemic colitis in the haemolytic-uraemic syndrome led to surgical complications of colonic necrosis or haemorrhage in 4 out of 62 patients treated during an 8-year period. Perforation occurred in the 2nd week of the illness and regular cultures of peritoneal dialysate fluid gave early warning of impending perforation. Persistent haemorrhage occurred late in the illness, and required surgical excision of the affected bowel. Offprint requests to: D. C. S. Gough     

Escherichia coli 0157: H7 infections associated with perforated appendicitis and chronic diarrhoea

Two unique associations of disease withEscherichia coli 0157H7 are presented. These cases broaden the spectrum of disease associated with this organism which currently includes bloody and non-bloody diarrhoea, haemolytic-uraemic syndrome, and thrombotic thrombocytopenic purpura.     

Adult respiratory distress syndrome associated withMycoplasma pneumoniae infection

A 13-year-old boy is described who developed severe adult respiratory distress syndrome (ARDS), biochemical pancreatitis and skin vasculitis after an acute respiratory infection due toMycoplasma pneumoniae. The boy was mechanically ventilated for 17 days, but could be discharged in good clinical condition after 36 days of hospitalization. However, major disturbances of the lung function tests persisted, suggesting interstitial fibrosis. To the best of our knowledge, this is the first case of ARDS afterM. pneumoniae infection in childhood.     

Bacterial genotype and neurological complications of Escherichia coli O157:H7-associated haemolytic uraemic syndrome

We examined the possibility of an association between the bacterial genotype of Escherichia coli O157:H7 and the likelihood of progression to neurological complications in childhood gastroenteritis-associated haemolytic uraemic syndrome (D+HUS). Bacterial stool isolates were available from 51 patients with HUS; 11 of these patients suffered a neurological complication. Bacteria were assessed for plasmid content, verotoxin (Shiga-like toxin) profile, verotoxin 2 subtype, and presence of the eaeA (effacement and attachment) marker. No association of bacterial genotype with central nervous system (CNS) manifestations was observed. Whilst the cause of CNS manifestions may be multifactorial, there is no evidence at present to implicate specific bacterial traits.     

Costello syndrome: clinical diagnosis in the first year of life

We report on three patients with Costello syndrome (CS) diagnosed during the first year of life and try to outline the clinical characteristics facilitating early recognition of this syndrome, which can now be corroborated by testing the HRAS gene. Phenotypical overlap of CS with Noonan (NS) and cardiofaciocutaneous syndrome (CFCS), particularly in neonatal age, is well known. Diagnostic features useful for recognition of CS in the first year of life are the following: (1) fetal and neonatal macrosomia with subsequent slow growth due to severe feeding difficulties, (2) developmental delay, (3) particularly coarse facial dysmorphisms and gingival hyperplasia, (4) skeletal anomalies as osteoporosis and metaphyseal enlargement, (5) hypertrophic cardiomyopathy (HCM) with asymmetric septal thickening and systolic anterior motion of the mitral valve, and (6) specific atrial arrhythmias. Following a clinical suspect of CS based on specific features, molecular screening of HRAS gene mutations should precede analysis of the other genes in the Ras-MAPK pathway implicated in related disorders with overlapping phenotypes.     

EnteropathognicEscherichia coli diarrhea in hospitalized children at Delhi

Prevalence of enteropathogenicE. coli (EPEC) in 4178 cases of acute diarrhea in hospitalised children of <2 years old admitted during 1980–1985 was studied.E. coli in pure culture was obtained from 15·5% of the stool samples. Of the isolates 58·8% were typable, however, only 43·2% belonged to known EPEC serotypes. The commonest serotype, was 020 (21·1%), followed by 018 (20·7%), 026 (8·8%), 0119 (8·4%), 0125 (7·7%), 086 (6·1%) and others. Majority of the serotypes were obtained from males and in the age group >6–12 months.     

Wrist anomalies in Turner syndrome compared with Leri-Weill dyschondrosteosis: a new feature in Turner syndrome

We analysed bone age radiographs in 102 girls with Turner syndrome and compared the findings with 93 control girls and nine girls with Leri-Weill syndrome. Various signs were analysed: radial bowing or Madelung deformity, maximal/minimal height of the radial epiphysis, brachymetacarpia of the 4th digit, carpal and epiphyseal angle, as well as a new sign the distal radio-ulnar physeal disparity. Two values differed significantly between the Turner group and the control group, the first being the epiphyseal angle which has already been reported to be greater in Turner syndrome, and the second being the new sign we have been able to describe. Turner patients had an increased distance between the ulnar and radial metaphysis, or distal radio-ulnar physeal disparity, the ulnar being shorter. Furthermore, in 27% of cases the medial extremity of the ulnar epiphysis was flattened and passed below the distal extremity of the radius, whose medial part projected over the distal extremity of the ulna, thus reproducing in reverse the characteristic feature of Leri-Weill syndrome. In the growth hormone-treated Turner patients, we found a significant correlation between distal radio-ulnar physeal disparity and growth velocity expressed in cm/year (r=0.28; P<0.002) or in SDS/bone age (r=0.21; P<0.03) during the first year of treatment. Conclusion: the value of this new sign requires further investigation.Abbreviations GH growth hormone - LWD Leri-Weill dyschondrosteosis - TS Turner syndrome Presented in part at the 41st Annual Meeting of the European Society for Paediatric Endocrinology.This revised version was published online in June 2004 with Table 1, which was inadvertently left out of the original version.     

Tetracycline-resistant <Emphasis Type="Italic">Escherichia coli</Emphasis> strains are inherited from parents and persist in the infant’s intestines in the absence of selective pressure

The study investigated tetracycline (TC), ampicillin (AMP), cefazolin (CEF), and trimethoprim (TMP) resistance in Escherichia coli (E. coli) in the feces of 21 infants up to 6 months of age and in their parents in the absence of selective antimicrobial pressure. Clonality of strains was assessed by pulsed-field gel electrophoresis. Three infants had resistant E. coli strains in their feces identical to the mothers’ from week 1 on, which persisted over weeks. From week 2 on, in another four infants, persisting resistant E. coli were found, two of them identical to the mothers’. All of these persisting E. coli strains (except one family) showed at least resistance to TC. In infants, resistant E. coli strains inherited from their mothers tended to persist over months. Therefore, the persistence of resistant E. coli and their possible capacity to cause symptomatic infection or transfer its resistance genes to other bacteria deserves more attention. Martina Prelog and Katharina Grif contributed equally to this work.     

Passive immunity acquisition of maternal anti-enterohemorrhagic Escherichia coli (EHEC) O157:H7 IgG antibodies by the newborn

Enterohaemorrhagic Escherichia coli (EHEC) strains are among the main causes of haemorrhagic colitis (HC) and haemolytic-uremic syndrome (HUS) in industrialised countries. In Brazil, EHEC have been detected in the faeces of patients with non-bloody diarrhoea, though an association between EHEC and HUS has been detected recently. These observations suggest that there is a pre-existing immunity triggered by the contact with EHEC and other categories of bacteria, such as EPEC, that share similar virulence factors and to which our population is highly exposed. Our aim was to evaluate the placental transfer of IgG antibodies reactive to EHEC O157:H7 antigens. We evaluated 28 paired maternal and cord sera for the presence of IgG against EHEC O157:H7 protein antigens and IgG and IgM to O157 LPS employing ELISA and IB technique. Total IgG and IgM level analyses were also made. Anti-EHEC O157:H7 and anti-LPS O157 IgG antibody levels in cord sera were equivalent to those of their maternal sera. A good correlation between the mothers’ anti-LPS O157 IgM and total IgM levels was found. Anti-LPS O157 IgM levels were higher than anti-LPS O157 IgG levels in the same samples, and anti-LPS IgM antibodies were not detected in cord sera. Identical patterns of recognition of bacterial protein antigens by specific IgG were found in the paired samples and the recombinant purified variable region of γ intimin was specifically recognized by one paired maternal and cord sample. In conclusion, although the antibody profile varied among individuals, all paired cord and maternal serum samples showed an identical recognition pattern, indicating an efficient placental transfer of IgG antibodies reactive to EHEC O157:H7 antigens. Dr. Patricia Palmeira and Leonardo Y. Ito contributed equally to this work.     

Simultaneous occurrence of the haemolytic uraemic syndrome and acute post-infectious glomerulonephritis

We report on two children, a 12-year-old boy and a 6-year-old girl, with simultaneous occurrence of clinical and laboratory features consistent with both diarrhoea-negative haemolytic uraemic syndrome (D-HUS) and acute post-infectious glomerulonephritis (APGN). Both presented with acute renal insufficiency, hypertension and oedema. Laboratory evaluation revealed micro-angiopathic anaemia with burr cells, thrombocytopenia, elevated lactic dehydrogenase and low complement C3. Urinalysis showed marked proteinuria and haematuria. Renal biopsy was characteristic of APGN, but not of HUS. The outcome was good in both children. Conclusion The simultaneous occurrence of diarrhoea-negative haemolytic uraemic syndrome and acute post-infectious glomerulonephritis is rare. The outcome is generally good as is expected in the latter condition in contrast to the former. Received: 10 August 2000 / Accepted: 20 September 2000     

The probiotic <Emphasis Type="Italic">Escherichia coli</Emphasis> strain Nissle 1917 (EcN) stops acute diarrhoea in infants and toddlers

In most cases, acute diarrhoea will become self-limiting during the first few days after onset. For young children, however, health risks may develop when the disease lasts longer than 3 days. The purpose of the present trial was to determine whether the stool frequency of infants and toddlers suffering from acute diarrhoea could be normalised more quickly by administering the probiotic Escherichia coli Nissle 1917 (EcN) solution than by administering a placebo. The safety of EcN were also assessed. A total of 113 children (aged 2–47 months) with acute diarrhoea (> three watery or loose stools in 24 h) were randomised to either a group receiving the probiotic EcN suspension (n = 55) or a group receiving the placebo suspension (n = 58) in a confirmative, double-blind clinical trial. Depending on the age of patients, 1–3 ml per day of verum suspension (10⁸ viable EcN cells per millilitre) or placebo were administered orally. The causes of the diarrhoea were viral rather than bacterial, but they were mainly unspecific infections. The median onset of treatment response (reduction of daily stool frequency to ≤ three watery or loose stools over at least 2 consecutive days) occurred more rapidly in the children receiving the EcN solution (2.5 days) than in those receiving the placebo (4.8 days), a significant difference (2.3 days; p = 0.0007). The number of patients showing a response was clearly higher (p < 0.0001) in the EcN group (52/55; 94.5%) than in the placebo group (39/58; 67.2%). EcN was found to be safe and well-tolerated, and it showed a significant superiority compared to the placebo in the treatment of acute diarrhoea in infants and toddlers. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. Supported by ARDEYPHARM through the provision of verum and placebo medication and reimbursement of study-related expenditure. The authors would like to thank all hospital staff members, clinical monitors and parents for contributing to the work achieved.     

Further delineation of the congenital form of X-linked dyskeratosis congenita (Hoyeraal-Hreidarsson syndrome)

Hoyeraal-Hreidarsson syndrome represents a severe variant of dyskeratosis congenita (Zinsser-Cole-Engman syndrome). This X-linked recessive, progressive, multisystemic disorder reported so far in 12 pedigrees is characterised by intrauterine growth retardation, microcephaly, cerebellar hypoplasia, mental retardation, progressive combined immune deficiency and aplastic anaemia. Mutations in the DKC1gene on Xq28 have been identified in the X-linked form of dyskeratosis congenita and in some Hoyeraal-Hreidarsson syndrome patients. We report on two sibs and two other unrelated patients with the striking clinical features of Hoyeraal-Hreidarsson syndrome. Noticeably, all four had early digestive problems, with chronic, bloody diarrhoea and feeding problems causing one of the most difficult problems in the supportive treatment of this uniformly lethal condition. Pathological changes in the proliferative compartment of the digestive mucosa included alterations of the glandular architecture and focal rarefaction of the glands. This aspect seems consistent with altered telomerase function associated with a dyskerin mutation which may decrease the proliferative capacity of digestive epithelial cells. A missense mutation 146 CT (Thr49Met) in the DKC1gene was found in two unrelated patients, whereas mutation screening was negative for one single case. The absence of mutations of the DKC1gene in patients with Hoyeraal-Hreidarsson syndrome emphasises the probable implication of one or more other loci.Abbreviations DC dyskeratosis congenita syndrome - HH Hoyeraal-Hreidarsson syndrome - IUGR intrauterine growth retardation