Infant botulism with prolonged faecal excretion of botulinum neurotoxin and Clostridium botulinum for 7 months.

In Finland in April 2010, a 3-month old baby was diagnosed with type A infant botulism. He excreted botulinum neurotoxin and/or Clostridium botulinum in his faeces until November 2010. Five months of excretion was after clinical recovery and discharge from hospital. C. botulinum isolates recovered from the household dust in the patient's home were genetically identical to those found in the infant's stool samples. Long-term faecal excretion of C. botulinum may pose a possible health risk for the parents and others in close contact with the infant.

A randomized, controlled trial of tonsillectomy in periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome.

OBJECTIVE: We carried out a prospective, randomized, controlled trial to clarify the effect of tonsillectomy on the clinical course of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome. STUDY DESIGN: Twenty-six consecutive children (mean age 4.1 years) with at least 5 PFAPA attacks were recruited from 3 tertiary care pediatric hospitals during 1999-2003 and randomly allocated to tonsillectomy or follow-up alone. They were all followed up with symptom diaries for 12 months. Tonsillectomy was allowed after 6 months in the control group if the attacks recurred. RESULTS: Six months after randomization all 14 children in the tonsillectomy group and 6/12 children in the control group (50%) were free of symptoms (difference 50%, 95% confidence interval 23% to 75%, P < .001). Tonsillectomy was performed on 5/6 of the patients in the control group who still had symptoms after 6 months. The remaining unoperated child in the control group had recurrences of the fever episodes throughout the follow-up, but the symptoms became less severe, and the parents did not choose tonsillectomy. CONCLUSION: Tonsillectomy appeared to be effective for treating PFAPA syndrome. The fever episodes ceased without any intervention in half of the control subjects. We conclude that although the mechanisms behind this syndrome are unknown, tonsillectomy can be offered as an effective intervention for children with PFAPA.

Replacing risk-based early-onset-disease prevention with intrapartum group B streptococcus PCR testing.

OBJECTIVE: To evaluate the effect of a rapid PCR-based group B streptococcus (GBS) test on length of stay in hospital among newborns, antibiotic use, and GBS-early-onset-disease (EOD) incidence. METHODS: We conducted a before and after service evaluation including term deliveries between 1st January and 12th November 2014 (6688 deliveries). Length of stay in the hospital, GBS-EOD incidence and antibiotic use were evaluated. RESULTS: We recorded three confirmed and 74 possible cases of GBS-EOD in Phase 1, and 85 possible cases in Phase 2. In newborns with suspected infection, the introduction of the rapid test was related to a decreased length of stay on the pediatric care unit by 1.16 days (p = 0.01), and an increase in the length of stay on the mother-and-baby ward by 1.11 days (p < 0.001). No increase in antibiotics was noted. CONCLUSION: The introduction of a point of care test was associated with a reduction in length of stay in the pediatric care unit, without an increase in antibiotic use. This test could improve the accuracy of GBS colonization detection, and help to prevent intrapartum transmission as no verified GBS-EOD cases were recorded with the intrapartum PCR algorithm.

Pharmacokinetics of fluconazole in very low birth weight infants during the first two weeks of life.

OBJECTIVE: To find a dose of fluconazole for very low birth weight infants during an outbreak of Candida parapsilosis. METHODS: Twelve premature infants (mean gestational age, 27.4 weeks; mean birth weight, 912 gm) receiving fluconazole prophylactically from the first day of life were enrolled in an open phase I-II pharmacokinetics, safety, and tolerance trial. Up to 5 doses of 6 mg/kg were administered intravenously every 72 hours during the first 2 weeks of life. Pharmacokinetic characteristics of fluconazole were determined after the first, third, and fifth doses. RESULTS: The mean peak and trough concentrations after the 3 doses were 5.5 and 2.6 micrograms/ml, 12.8 and 4.3 micrograms/ml, and 10.0 and 2.9 micrograms/ml (p = 0.0002 and p = 0.07), respectively. The mean fluconazole half-lives were 88.6 hours (n = 7), 67.5 hours (n = 9), and 55.2 hours (n = 4; p = 0.3). The mean total clearance corrected for weight (CL/kg) was 0.18 ml/min/kg (n = 7), 0.33 ml/min/kg (n = 7), and 0.52 ml/min/kg (n = 4; p = 0.02), and the mean volume of distribution 1.18 L/kg (n = 7), 1.84 L/kg (n = 7), and 2.25 L/kg (n = 4; p = 0.05). Weight-corrected clearance increased with postnatal age (r = 0.61; p = 0.007). CONCLUSIONS: With the used fluconazole dose (6 mg/kg every 3 days), the mean serum peak and trough concentrations increased during the first week but decreased during the second week. After the first week we suggest a dose of 6 mg/kg every 2 days, or even daily.

Detection of Haemophilus ducreyi lipooligosaccharide by means of an immunolimulus assay.

A murine monoclonal antibody (MAb) directed against a surface-exposed epitope of the lipooligosaccharide (LOS) of Haemophilus ducreyi strain 35000 was shown to be reactive with all 37 strains of this pathogen tested in a colony blot-radioimmunoassay. The LOS epitope bound by this MAb appeared to be stably expressed by H. ducreyi growing in vitro. The use of this MAb in the immunolimulus system revealed that it could detect purified H. ducreyi LOS at a level of 25 pg/ml. Similarly, this immunolimulus system could detect as few as 1000 colony forming units of in vitro-grown H. ducreyi cells per ml of buffer. When this MAb was utilized in the immunolimulus system together with lesion material from rabbits infected with two different H. ducreyi strains, a positive reaction was obtained with every sample tested, even when no viable organisms were present in the lesion material. In contrast, this MAb yielded consistently negative results when used in the immunolimulus system with lesion material from animals infected with Staphylococcus aureus.

Single-dose and steady-state pharmacokinetics of a new oral suspension of ciprofloxacin in children.

OBJECTIVE: Quinolones are used ever increasingly in pediatrics, although officially they are still contraindicated. Lack of evidence of arthropathic effects in human offspring favors their use, but little is known about the pharmacokinetics of oral or parenteral ciprofloxacin in children, especially those without cystic fibrosis. DESIGN: We studied 16 non-cystic fibrosis patients ranging in age from 0.3 to 7.1 years to whom the new suspension formulation of ciprofloxacin (10 mg/kg body weight) was given orally three times daily. Single-dose and steady-state pharmacokinetic parameters were elucidated. RESULTS: Ciprofloxacin was rapidly absorbed. The maximum plasma concentrations, with the means varying from 1.7 to 3.6 mg/L, were reached within 1 hour, almost regardless of whether single-dose administration or steady state. The mean oral clearance was lower in children <6 years of age than in those >/=6 years. Terminal half-life values, with the means varying only between 4.2 and 5.1, suggest that dosing recommendations based on body weight are pertinent, although caution should be exercised in small infants. No arthropathic or other adverse events attributable to ciprofloxacin suspension were observed. CONCLUSION: A dose of the suspension form of ciprofloxacin of 10 mg/kg body weight given orally three times daily seems appropriate in children, provided the drug is clearly indicated.

The protective capacity of immune sera in experimental mouse salmonellosis is mainly due to IgM antibodies.

Passive immunization was used to protect mice against a general infection caused by Salmonella typhimurium and our purpose was to compare the protective capacity of different immunoglobulin isotypes (classes and subclasses). Three antisera were studied, one pool of mouse serum against the envelope of rough bacteria, and two rabbit sera against smooth bacteria. Three different methods were used to separate isotypes. The consistent finding was that only IgM antibodies protected efficiently. A unit of IgG antibodies had an effect that was 1/50th of the IgM effect or less. This effect could have been due to a contamination by IgM. IgA appears to be non-protective like IgG. In two of the antisera a considerable proportion of protective antibodies were against a defined antigenic determinant (anti-0-4,5 or anti-0-9). IgG antibodies of these sera measured by the solid phase assay were also predominantly anti-0-4,5 or anti-0-9, respectively. This argues that the failure of IgG antibodies to protect cannot be explained by assuming that unlike IgM antibodies they are directed against "non-protective" determinants. We conclude that the observed difference between the protective capacities of IgM and IgG antibodies is due to C-region differences between the mu- and gamma-chains.

Salmonella, complement and mouse macrophages.

The structure of the polysaccharide chains that constitute the O antigen on the surface of Salmonella bacteria determines the rate of complement activation and C3b deposition on the bacteria. A fast-activating O antigen causes rapid C3-dependent opsonization of the bacteria injected intraperitoneally; as a consequence, the bacteria are taken up and killed by the resident peritoneal macrophages, and their virulence is low. A slow-activating O antigen protects the bacteria from opsonization in the peritoneal cavity, and is associated with higher virulence. However, if injected intravenously bacteria with either O-antigenic type are equally virulent; in the high complement concentration of the blood they become opsonized and taken up by macrophages in the liver and spleen, which are unable to kill them but instead provide a protected site for multiplication.

Randomized, placebo-controlled double blind study on the efficacy of influenza immunization on absenteeism of health care workers.

BACKGROUND: In healthy adults influenza immunization reduces absenteeism caused by respiratory infections, but data on its efficacy among health care workers are scarce. OBJECTIVE: To determine the effect of the conventional inactivated influenza A vaccine on reducing absenteeism related to respiratory infections among pediatric health care providers. STUDY DESIGN: A randomized, placebo-controlled, double blind study on vaccine efficacy was conducted in two pediatric hospitals during the winter season 1996 to 1997. The primary endpoint was days of work lost from the hospital because of respiratory infections. The documentation of absenteeism was based on personal sickness logs. RESULTS: Of the 547 randomized vaccinees 427 (78%) persons completed the 4-month follow-up and returned the sickness logs. Immunization failed to reduce episodes of respiratory infections (1.8 episodes/study period among vaccinees vs. 2.0 among controls). Similarly the vaccine failed to affect the total number of days the vaccinees suffered from respiratory infections (13.5 days vs. 14.6 days, respectively). However, days of work lost because of respiratory infections (1.0 days vs. 1.4 days, respectively, P = 0.02) and especially total numbers of days the study persons felt themselves unable to work when either on or off duty (2.5 days vs. 3.5 days, P 0.02) were significantly decreased. CONCLUSION: Influenza vaccination reduced absenteeism related to respiratory infections by 28%. We therefore believe that routine annual influenza immunizations should be recommended to health care providers working in pediatric settings.

Bacteriology of histopathologically defined appendicitis in children.

BACKGROUND: Acute appendicitis is the most common surgical emergency in childhood. However, the pathogenesis and detailed microbiology are obscure. OBJECTIVE: To determine in detail the bacterial etiology of appendicitis in children in relation to the histologic tissue pathology. STUDY DESIGN: Tissue samples obtained at surgery from 41 children with suspected acute appendicitis were examined histologically and by culture for aerobic and anaerobic bacteria. The patients were analyzed according to histopathologic and clinical findings. RESULTS: Aerobic and anaerobic species were isolated from 40 of 41 (98%) samples; on average, 14.1 isolates per specimen (10.4 anaerobes and 3.7 aerobes). Specimens from patients with gangrenous appendices yielded significantly higher numbers of anaerobic isolates per specimen than did specimens from patients with healthy appendices (11.7 vs. 7.7; P < 0.01). Bacteria belonging to the Bacteroides fragilis group were the most frequently isolated anaerobic microorganisms (95%). Other organisms frequently isolated in all histology groups were Peptostreptococcus micros (66%), Bilophila wadsworthia (63%), Fusobacterium nucleatum (44%), Eggerthella lenta (44%) and a hitherto undescribed bile-resistant, pigment-producing Gram-negative rod (41%). Of the aerobes Escherichia coli (88%) and Streptococcus anginosus group (former Streptococcus "milleri" group) organisms (61%) were the most frequent findings. CONCLUSIONS: The shift from histologically normal toward gangrenous appendices was clearly associated with markedly elevated anaerobic bacterial counts in terms of species. The unusually high frequencies of B. wadsworthia (75%) and the hitherto undescribed bile-resistant, pigment-producing Gram-negative rod (56%) in gangrenous appendices represent unique and different findings from those reported in adults.

Neonatal Candida parapsilosis outbreak with a high case fatality rate.

A Candida parapsilosis outbreak of 58 cases in a neonatal intensive care unit lasted for 55 months. Patients infected by or colonized with C. parapsilosis were mainly very low birth weight infants (birth weight < 1500 g). Their mean birth weight was 817 g and their mean gestational age was 28 weeks. Statistical analysis including logistic regression confirmed that prematurity was the main risk factor. The analysis also suggested that C. parapsilosis infection (or colonization) was associated with a poor prognosis. In infants with gestational age < 29 weeks the risk for death in C. parapsilosis-infected patients was 16-fold greater than in those with no C. parapsilosis infection. The case fatality rate of C. parapsilosis patients was higher than that of the controls (9 of 23 vs. 1 of 40; P < 0.0001). The outbreak was most likely a result of cross-infection because C. parapsilosis could be isolated only from the patients and from the hands of four nurses immediately after they had cared for a colonized patient. Cessation of the outbreak was temporally associated with long term parenteral fluconazole (6 mg/kg/day) prophylaxis.

Predictive factors associated with significant urinary tract abnormalities in infants with pyelonephritis.

BACKGROUND: Major urinary tract abnormalities are detected in 20 to 40% of infants with acute pyelonephritis (APN). Early detection of structural defects is essential for protecting the kidneys from reinfection and subsequent scarring. The purpose of this study was to investigate whether any factors present during the acute phase of infection could predict the presence of existing significant urinary tract abnormalities in infants. METHODS: A prospective study of 180 infants, aged 1 to 24 months, with APN was conducted. Blood and urine samples were collected. Renal ultrasound (US) was performed within 0 to 6 days from admission. Final diagnosis of the urinary tract anatomy was elucidated using the results of two or more radiologic imaging studies. RESULTS: Risk factors for the presence of significant urinary tract abnormalities in infants were pathogens other than Escherichia coli in urine [relative risk (RR) 3.4, 95% confidence interval (CI) 2.2 to 5.3; P = 0.001], positive blood culture (RR 2.3, 95% CI 1.3 to 4.0; P = 0.039), young age (1 to 6 months) (RR 2.2, 95% CI 1.3 to 3.9; P = 0.004), lack of papG adhesin genes of E. coli in urine (RR 2.1, 95% CI 1.2 to 3.9; P = 0.016) and abnormal renal US (RR 2.0, 95% CI 1.2 to 3.4; P = 0.008). CONCLUSIONS: Infants 1 to 6 months of age with APN caused by bacteria other than E. coli or by papG-negative E. coli strain, positive blood culture and abnormal renal US carry an increased risk for significant urinary tract abnormalities and need enforced follow-up.

Invasive fungal infections in pediatric bone marrow transplant recipients: single center experience of 10 years.

Invasive fungal infections (IFI) with substantial mortality constitute an increasing problem among BMT patients. From 1986 to 1996 148 children underwent BMT, and are included in a retrospective analysis of the incidence, risk factors and outcome of IFI. By histopathology or culture-proven IFI (Candida, 10; Aspergillus, 8) was documented in 12/73 (16%) allogeneic and in 6/75 (8%) autologous BMT patients. Of these 18 patients, 15 subsequently died, and in 12 (66%) IFI was regarded as the main cause of death. In addition to the patients with documented IFI, 48 had suspected and 82 no fungal infection. Invasive candidal infections were more frequent in patients with semiquantitatively estimated abundant candidal colonization as compared with those with no colonization (18% vs 3%, P = 0.015). In the allogeneic group, 50% of those with severe (grades III-IV) aGVHD had IFI as opposed to 8% of those with no or mild aGVHD (P < 0.001). Regarding cGVHD, 57% of those with extensive cGVHD vs 5% of those with absent or limited cGVHD had IFI (P < 0.001). The dose of steroids was associated with IFI: 77% of those who received high-dose steroids (methylprednisolone 0.25-1 g/day for 5 days) vs 5% of those with conventional-dose (prednisone 2 mg/kg/day) had IFI (P < 0.001). Particularly for BMT patients at risk, new, quicker and better diagnostic tests and more effective anti-fungal agents, both for prophylaxis and treatment, are needed.

Protective capacity of antibodies to outer-membrane components of Escherichia coli in a systemic mouse peritonitis model.

Antibody-mediated protection was studied in an experimental murine model of peritonitis-septicaemia with Escherichia coli O18:K1. Protection from lethal intraperitoneal challenge was achieved by passive immunisation with horse anti-K1 capsular antiserum (H46) or rabbit antiserum to the homologous O18 antigen. The maximum increase in LD50 achieved with anti-K1 and anti-O18 antibodies was 10- and 5-fold, respectively. The protective capacity of the anti-O serum was found to be in the IgG fraction. Rabbits were also immunised with various semi-purified or purified outer-membrane-protein preparations (porins and OmpA protein) from rough E. coli or Salmonella strains or with whole E. coli J5 bacteria. Although this immunisation resulted in high antibody titres to homologous and, to a lesser extent, also to heterologous antigens, none of the antisera protected against challenge with the capsulate E. coli O18:K1 bacteria.

Genomic identity of pyelonephritogenic Escherichia coli isolated from blood, urine and faeces of children with urosepsis.

Chromosomal genotypes of Escherichia coli isolates from blood, urine and faeces of infants with urosepsis were studied to find possible clonality of the isolates. The isolates were analysed by PCR for class I, II and III alleles of the pyelonephritis-associated adhesin gene papG. The macrorestriction profiles of the papG-positive isolates were analysed by pulsed-field gel electrophoresis and their O serogroups were determined. Genetically identical E. coli isolates from the blood, urine and faeces of the same infant were found in 8 of 10 infants. This finding confirmed the results of previous phenotypic studies that the reservoir of pyelonephritogenic E. coli is indeed the colon.

Using feed-forward neural networks for estimation of microbial concentration in a simulated biochemical process.

This work investigated the feasibility of using feed-forward neural networks for estimation of a state variable in a process with highly non-linear characteristics. A biochemical process was considered where the microorganism Saccharomyces cerevisiae, a yeast, grows in a chemostat on a glucose substrate and produces ethanol as a product of primary energy metabolism. Three state variables for the process are the microbial concentration, substrate concentration and product concentration. The Levenberg-Marquardt Method was used to train the neural networks by minimising the sum of squares of the residuals. The inputs to the networks were the measured variable (product concentration) and the control variable (dilution rate). The output of the network was an estimate for the microbial concentration. Earlier work had shown that system identification of this biochemical process could be performed quite well using feed-forward neural networks. This work demonstrated that state estimation can also be performed successfully using feed-forward neural networks. Knowledge of the process model is not required. The method is simple, reliable and accurate enough for engineering purposes. It can save a lot of expense on sensors, their installation and maintenance.

Biological characterization of Campylobacter fetus lipopolysaccharides.

Lipopolysaccharides (LPS) of three strains of Campylobacter fetus (subspp. fetus and venerealis, and serotypes A and B), a bacterium of veterinary importance but also a cause of various infections in humans, were assessed for their ability to induce mitogenicity, gelation of Limulus amebocyte lysate, lethal toxicity in mice, and pyrogenicity in rabbits. All C. fetus LPS exhibited activities lower than those of Salmonella typhimurium LPS. LPS of C. fetus subsp. fetus serotype A had the lowest activity in all assays. Since the majority of C. fetus subsp. fetus isolates from humans are serotype A, the lower biological activities of this LPS may aid the pathogenesis of such strains. The lower activities of C. fetus LPS compared with those of S. typhimurium LPS may reflect the presence of longer fatty acid chains in the lipid A of C. fetus LPS, whereas interstrain differences in C. fetus LPS bioactivities may be related to some property influenced by composition of the saccharide moiety.

Group A streptococcal outbreak of perianal infection in a day-care centre.

Within 9 days in a day-care centre of 20 children 3 cases and 2 suspected cases of perianal infection (PAI) were revealed. The causative agent for PAI was confirmed to be beta-haemolytic group A streptococcus (GAS). The isolates were further characterized by T- and M-serotyping, conventional restriction endonuclease analysis (REA) and pulsed field gel electrophoresis (PFGE). The typing methods revealed that all outbreak isolates were of same T28R28-serotype and genetically identical. Unrelated, control GAS isolates of the same serotype differed genetically from the outbreak isolates indicating that a single clone had caused the perianal infections.

Surgical treatment of intractable cholestasis associated with total parenteral nutrition in premature infants.

We report surgical reversal of intractable total parenteral nutrition (TPN)-associated cholestasis refractory to conservative treatment in 9 premature infants. Indications for TPN were poorly tolerated enteral feedings in all patients. Five patients had undergone gastrointestinal operations; in addition, 7 of the 9 patients had had bacterial sepsis. The median duration of TPN was 28 days (range, 20 to 50 days). The median duration of preoperative full enteral nutrition after weaning from TPN was 34 days (range, 16 to 95 days). All patients had progressive conjugated hyperbilirubinemia, no excretion of Tc-labeled HIDA to the biliary tree and duodenum, and markedly elevated liver enzyme values. Intraoperative cholangiography showed normal biliary anatomy in all cases; in addition, 2 patients had gallbladder stones. Bile was hyperviscous in all patients and contained biliary sludge in 4. The biliary tree was irrigated and the liver biopsied in all patients. The gallbladder was removed from 2 patients who had stones in the gallbladder. Liver histology was consistent with TPN-associated cholestasis in all cases, and in addition, 4 cases showed significant destruction of intrahepatic bile ducts. One patient died 2 weeks postoperatively from intracerebral hemorrhage. Jaundice completely resolved in other patients within 2 weeks. HIDA-biligraphy performed 1 to 2 months postoperatively showed normal excretion of the radioactive marker to the biliary tree and duodenum in all cases. The functional abnormality in bile excretion and bile duct motility in TPN-associated cholestasis may be reversed by irrigation of the biliary tree. Surgical intervention should be considered when cholestasis is progressive and refractory to medical management.

Unilateral blindness in a child with acute sinusitis.

Orbital infection in association with sinusitis is an emergency. It may cause visual disturbances, and in rare cases even permanent blindness by affecting the optic nerve. We report an unusual case of acute sinusitis that was complicated by irreversible visual loss in a young patient. As there is increasing evidence that respiratory viruses play an important role in the pathogenesis of acute community acquired sinusitis and spontaneous healing with only symptomatic treatment is common, the use of antibiotics in the treatment of acute sinusitis may not be needed in all cases. If the general policy to use antibiotics in acute sinusitis will be changed to more restrained and expectant, we have to be even more aware of these nowadays rare complications.