A possible murine model for investigation of pathogenesis of sudden infant death syndrome.

Several studies have indicated a possible causative role of toxigenic bacteria in sudden infant death syndrome (SIDS). This study examined the effect of toxigenic E. coli on pregnant and infant mice to determine if these animals could be used as a model for SIDS pathogenesis. Strains of E. coli from the intestinal contents of infants who have died of SIDS or other causes and from the faeces of healthy infants were collected over a broad time scale. The isolates were tested for their ability to produce then known toxins of E. coli and were serotyped (O and H antigens). Certain serotypes (e.g. O1:H- and O25:H1) emerged significantly more frequently from cases of SIDS than from healthy infants and isolates of these types were generally toxigenic in Vero-cell cultures but whose verotoxicity was not related to classical Shiga or other known toxins. This mouse model was developed to test the effects of these toxigenic and also non-toxigenic strains. Four apparently healthy pups aged between 17 and 21 days died unobserved overnight but no pups of the 54 control mice died suddenly (P = 0.0247, Fisher's exact test). These were considered to represent sudden unexpected deaths. Pathological effects compatible with those in SIDS were observed in mouse pups exposed to toxigenic strains indicating this model may be suitable for further study into the pathogenesis of unexpected deaths in infancy. Providing an animal model of SIDS would promote a much better avenue for studying the pathogenesis of this enigmatic condition.

Serotypes of Escherichia coli in sudden infant death syndrome.

AIM: To examine the diversity of Escherichia coli serotypes found in the intestinal contents of infants who died of Sudden Infant Death Syndrome (SIDS) compared with that in comparison infants. METHODS AND RESULTS: Over the 3-year period, 1989-1991, in South Australia and Victoria (Australia), a total of 687 E. coli isolates from 231 patients with SIDS (348 isolates), 98 infants who had died from other causes (144 isolates) and 160 healthy infants (195 isolates) were studied. The isolates from patients with SIDS were found to represent 119 different serotypes; the isolates from 'other cause' infants represent 97 different serotypes; and the isolates from healthy infants represent 117 different serotypes. The seven common serotypes isolated most frequently from infants with SIDS belonged to those associated with extra-intestinal infections in humans. Compared to healthy infants (6%), these were found in significantly higher proportions among infants who died of other causes (13%, P < 0.05) or infants with SIDS (18.7%, P = 0.0002). CONCLUSIONS: Despite these sources yielding a wide variety of serotypes of E. coli, a pattern of certain potential pathotypes of E. coli being associated with SIDS is apparent. SIGNIFICANCE AND IMPACT OF THE STUDY: While SIDS remains one of the most important diagnoses of postneonatal death, its causes are still unexplained. If E. coli has a role in the pathogenesis of SIDS (as suggested by the pathotypes identified on the basis of serotype), further studies may reveal novel virulence factors that may clarify the role of this bacterium in SIDS.

Fetal exposure to herpesviruses may be associated with pregnancy-induced hypertensive disorders and preterm birth in a Caucasian population.

OBJECTIVE: To investigate the role of fetal viral infection in the development of a range of adverse pregnancy outcomes (APOs), including pregnancy-induced hypertensive disorders (PIHD), antepartum haemorrhage (APH), birthweight <10th percentile (small for gestational age, SGA) and preterm birth (PTB). DESIGN: Population-based case-control study. SETTING: Laboratory-based study. POPULATION: The newborn screening cards of 717 adverse pregnancy cases and 609 controls. METHODS: Newborn screening cards were tested for RNA from enteroviruses and DNA from herpesviruses using polymerase chain reaction (PCR). The herpesviruses were detected using two PCRs, one detecting nucleic acids from herpes simplex virus (HSV)-1, HSV-2, Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human herpesvirus (HHV)-8, hereafter designated Herpes PCR group A viruses, and the other detecting nucleic acids from varicella-zoster virus (VZV), HHV-6 and HHV-7, hereafter designated Herpes PCR group B viruses. MAIN OUTCOME MEASURE: Odds ratios and 95% CIs for specific APOs. RESULTS: For both term and PTBs, the risk of developing PIHD was increased in the presence of DNA from Herpes PCR group B viruses (OR 3.57, 95% CI 1.10-11.70), CMV (OR 3.89, 95% CI 1.67-9.06), any herpesvirus (OR 5.70, 95% CI 1.85-17.57) and any virus (OR 5.17, 95% CI 1.68-15.94). The presence of CMV was associated with PTB (OR 1.61, 95% CI 1.14-2.27). No significant association was observed between SGA or APH and exposure to viral infection. CONCLUSIONS: Fetal exposure to herpesvirus infection was associated with PIHD for both term and PTBs in this exploratory study. Exposure to CMV may also be associated with PTB. These findings need confirmation in future studies.

Association between rotavirus infection and pancreatic islet autoimmunity in children at risk of developing type 1 diabetes.

Pancreatic islet autoimmunity leading to type 1 diabetes could be triggered by viruses in genetically susceptible individuals. Rotavirus (RV), the most common cause of childhood gastroenteritis, contains peptide sequences highly similar to T-cell epitopes in the islet autoantigens GAD and tyrosine phosphatase IA-2 (IA-2), suggesting T-cells to RV could trigger islet autoimmunity by molecular mimicry. We therefore sought an association between RV infection and islet autoantibody markers in children at risk for diabetes who were followed from birth. There was a specific and highly significant association between RV seroconversion and increases in any of these antibodies: 86% of antibodies to IA-2, 62% to insulin, and 50% to GAD first appeared or increased with increases in RV IgG or IgA. RV infection may therefore trigger or exacerbate islet autoimmunity in genetically susceptible children.

Apparent non-involvement of prions in the pathogenesis of spongiform change in HIV-infected brain.

Characteristic neuropathological white matter changes in the brains of patients dying from the acquired immune deficiency syndrome (AIDS) suggest pathogenetic involvement of either the PrP27-30 gene or a scrapie-related prion; however, proteinase-K resistant scrapie-like proteins could not be detected in brain tissue from AIDS patients.

Sequence of a variant Shiga-like toxin type-I operon of Escherichia coli O111:H-.

PCR amplification was used to screen faecal isolates of Escherichia coli from a 12-month-old boy with haemolytic uraemic syndrome for the presence of Shiga-like toxin (SLT)-encoding genes. One isolate, belonging to serotype O111:H-, was positive for SLT-I by this method. UV induction indicated that the strain was lysogenic for a lambdoid bacteriophage, but this did not encode the toxin. Southern hybridization analysis of chromosomal DNA revealed that the SLT-I gene was located on an 8.5-kb EcoRI fragment. SLT-I was further localized to within a 3.0-kb SphI-EcoRI fragment. A separate subclone contained a 3.75-kb HindIII fragment, 1.18 kb of which was common to both. Nucleotide sequence analysis of derivatives of these clones revealed that the SLT-I A subunit gene from E. coli O111:H- differed from the previously published sequences for SLT-I by 5 bp [resulting in two amino acid (aa) changes]. It was more closely related to the gene encoding the A subunit of the Shiga toxin from Shigella dysenteriae type 1, from which it differed by 3 bp (resulting in one aa change). The DNA sequence of the B subunit-encoding gene was identical to that of the other two toxins. The region of DNA upstream from the SLT-I of E. coli O111:H- contained an IS element, as well as a region with strong homology to a portion of the genome of bacteriophage lambda.

Impact of a recapping device on venepuncture-related needlestick injury.

In a 33-month prospective analysis of needlestick injuries, venepuncturists working under Centers for Disease Control (CDC) guidelines for handling used needles were shown to incur a needlestick injury for every 3,175 to 4,006 needle-handling procedures. On the other hand, users of a simple device designed to reduce the risk of injury when recapping used needles were shown to incur a needlestick only once in every 16,100 venepunctures performed (P less than 0.001). This represents a fourfold reduction in the rate of needlestick injuries. We thus question the effectiveness of the CDC nonrecapping policy.

A survey of nosocomial respiratory viral infections in a children's hospital: occult respiratory infection in patients admitted during an epidemic season.

OBJECTIVE: To define the extent of shedding of respiratory viruses and Mycoplasma pneumoniae among a population of pediatric patients admitted to the hospital during a winter epidemic period and to identify nosocomial infections within this population. DESIGN: An open, prospective survey of patients admitted to three wards (General Medical, Respiratory Infectious, and Infectious Diseases) of a pediatric hospital during a defined three-month period. PATIENTS: All patients with medical, respiratory, and infectious conditions admitted to three wards of the Adelaide Children's Hospital had nasopharyngeal aspirations performed at the time of admission with the purpose of documenting viral and M pneumoniae shedding. Patients were monitored daily for the development of symptoms of respiratory infection or new symptoms of respiratory disease. Such patients underwent a further nasopharyngeal aspiration for the purpose of diagnosing hospital-acquired infection. RESULTS: Nasopharyngeal aspirations were obtained from 601 patients. Forty-seven percent of asymptomatic patients were positive for a respiratory virus or M pneumoniae, and 61% of patients with respiratory symptoms were also positive. Gastroenteritis patients shed viruses in 66% of cases. Respiratory symptoms were initially overlooked by admitting physicians but subsequently identified in 110 cases, and 46% of these were found to be positive for a respiratory virus or M pneumoniae. There were 18 possible hospital acquired infections among the 293 initially virus-negative patients. Multiple isolates were obtained from a substantial number of patients, especially those with respiratory symptoms. CONCLUSIONS: A substantial proportion of all patients admitted to a pediatric hospital during winter represent a potential source of infection, and strict infection control measures should be enacted to limit the spread of these infections.

New perspectives on the role of Escherichia coli O157:H7 and other enterohaemorrhagic E. coli serotypes in human disease.

This review compares the rates of detection of non-O157:H7 enterohaemorrhagic Escherichia coli (EHEC) with EHEC O157:H7 in outbreaks and sporadic cases of human disease by analysing Australian data and the world literature. Numerous outbreaks of disease have been attributed to EHEC O157:H7. In many studies, isolation rates of this organism have been low and attempts to seek other EHEC have not been made. Ease of isolation and identification of the O157:H7 serotype may have given the impression that this serotype was the sole organism responsible for the outbreaks. Careful review and analysis shows that serotypes other than O157:H7 also play an important role in human disease. Evidence is presented from several overseas outbreaks described in the literature, as well as from investigations of the Adelaide O111:H- outbreak, that suggests an association between severity of disease and multiple infecting serotypes. While not diminishing the role of the O157:H7/H- clone, this review indicates that other serotypes can be responsible for outbreaks as well as cases of sporadic human disease. The current focus on O157:H7 has major implications in terms of diagnosis, the food industry and human health.

Solid-phase immunosorbent haemadsorption (SPIHAd): a new, rapid and simple test for rubella-specific IgM.

A new, rapid and highly sensitive test for rubella-specific IgM not requiring pretreatment of serum for removal of non-specific inhibitors and heteroagglutinins was developed and compared with sucrose density gradient fractionation/haemagglutination inhibition. The test was shown to be highly sensitive in detecting rubella-specific IgM resulting from natural infection, but gave variable results in detection of rubella vaccine-induced IgM. The advantages of the solid-phase immunosorbent haemadsorption (SPIHAd) test are its rapidity, inexpensiveness, the large number of untreated whole sera that can be handled at one time, and the lack of interference by rheumatoid factor and by rubella-specific IgG.

An unusual case of microangiopathic haemolytic anaemia associated with enterohaemorrhagic Escherichia coli O113:H21 infection, a verocytotoxin-2/shiga toxin-2 producing serotype.

A case of microangiopathic haemolytic anaemia and thrombocytopaenia in a 79-year-old woman is presented. The case is unusual in that diarrhoeal symptoms were brief and symptoms of anaemia caused her to re-present to hospital 6 days after the diarrhoea had ceased. Enterohaemorrhagic Escherichia coli O113:H21 producing shiga toxin-2 was isolated from a faecal specimen. This serotype has been reported only a few times to be associated with serious disease. However, it is amongst the 20 most common serotypes carried in cattle and found in beef. This case also illustrates the importance of using shiga-toxin gene detection in faecal cultures (as opposed to cultural methods for detection of the O157:H7 serotype) as the recommended investigation of human disease for accurate epidemiology and attribution of cause.

Distribution of toxigenic Escherichia coli serotypes in the intestines of infants.

As part of an ongoing study into the pathogenesis of sudden infant death syndrome (SIDS), the distribution of serotypes of toxigenic and non-toxigenic Escherichia coli within the gastrointestinal tract of babies who had died was investigated. Escherichia coli isolates from the mid-ileum, colon and rectum of six SIDS cases and one case which had died suddenly and unexpectedly but had underlying cardiac pathology were "O" serogrouped and examined for verocytoxic activity and production of heat-labile enterotoxin. In addition, the effect of storage of gut specimens and rectal swabs at 4 degrees C on isolation of toxigenic strains was studied in three of the cases. A diversity of serogroups and toxigenicity was a general finding, however, strains found in the proximal gut were also cultured from the rectum, indicating that faecal specimens would be a valid tool in investigating the role of these organisms in SIDS cases compared with healthy controls. Storage for up to 5 days at 4 degrees C had no appreciable effect on isolation rates of toxigenic bacteria.

The isolation of cytotoxic necrotizing factor (CNF)-producing Escherichia coli from the intestinal contents of babies who died of sudden infant death syndrome (SIDS) and other causes as well as from the faeces of healthy babies.

Strains of Escherichia coli producing cytotoxic necrotizing factor (CNF) have been isolated from intestinal contents of 16.8% of babies who died of Sudden Infant Death Syndrome (SIDS) and 16.5% of faeces from healthy babies. While no difference in CNF carriage was seen, it is noteworthy that these CNF-producing E. coli are present in such specimens. Some of the CNF-producing E. coli belonged to serotypes associated with this factor in other parts of the world.

Echovirus 19 outbreak in Auckland 1975-76.

An epidemic of echovirus 19 infection in Auckland, New Zealand, during the summer of 1975-76 is reported. Echovirus 19 was recovered from 33 patients, 70 percent of whom had upper respiratory tract involvement, 55 percent presented with meningitis and 33 percent exhibited a rash. Gastroenteritis was diagnosed in 9 percent. Various clinical syndrome combinations were common. The overall male to female ratio was one. Infants younger than six months were more seriously affected than older patients.

Chronic chest wall sinus: an unusual presentation of typhoid.

A chronic discharging sinus of the chest wall is described in a 59-year-old Maori woman investigated as a typhoid contact. A heavy growth of Salmonella typhi organisms was cultured from the sinus, which had first appeared 13 years previously.

Acute viral hepatitis in Auckland.

A community survey was undertaken in order to determine the seroepidemiologic pattern of acute viral hepatitis in Auckland. As hospital records and Health Department notifications underestimate the problem, all patients with a serum alanine transpeptidase (ALT) level of greater than 200 mu/l (X 5 normal) were investigated for viral liver disease. Over a four month period a total of 303 cases of acute viral hepatitis were identified, 49 (16.2%) were hepatitis A, 11 with coincident hepatitis B, 88 (29%) were hepatitis B, 80 (26.4%) nonA nonB hepatitis, 81 (26.7%) Epstein Barr virus hepatitis and 5 (1.6%) cytomegalovirus hepatitis. Hepatitis A and hepatitis B occurred with increased frequency among Maoris and Polynesians, while Epstein Barr virus, cytomegalovirus and nonA nonB hepatitis occurred more frequently among Europeans. The incidence of acute symptomatic viral hepatitis (excluding cytomegalovirus and Epstein Barr virus infections) was 78 cases/10(5)/per year for the Auckland region in this survey.

Mononucleosis-like-syndrome associated with acute AIDS retrovirus infection.

A 47-year-old man developed an acute infectious mononucleosis-like illness with a moderate lymphocytosis and numerous atypical lymphocytes in the peripheral blood. Seroconversion to the AIDS-associated virus occurred between 14 and 20 days following the onset of the acute illness. He was found to have reduction of the T4:T8 ratio, low mitogenic response to PHA and cutaneous anergy when tested at 25 and 136 days. These tests had returned to normal by 262 days.

Intradermal, low dose, short course hepatitis B vaccination.

Seventy-five of 88 (85.2%) vaccinees seroconverted at three months after three 2 micrograms doses of a plasma-derived hepatitis B vaccine had been given intradermally one month apart. Vaccinees under 30 years of age had a significantly better seroconversion rate (88.8%) than older subjects (50%) as measured at three months. Forty-three of 47 (91%) vaccinees who were bled one year post vaccination had antibody levels in excess of 10 IU/1. This study indicates that short course, low dose, intradermal vaccination with plasma-derived hepatitis B vaccine may be a viable and cheap regimen for inducing immunity against hepatitis B in younger subjects.

Which antibiotic and when.

Initial empirical antibiotic therapy for infection requires knowledge of the likely causative organism and its expected antibiotic susceptibilities. By definition, initiation of such therapy is required before culture results are available. Although antibiotic therapy appears complex and confusing owing to the ever increasing list of new agents, the factors to consider before choosing an antibiotic remain the same. This article looks at these factors and presents treatment choices for some common infections.