Whole-genome sequencing in the investigation of recurrent invasive group A streptococcus outbreaks in a maternity unit.

BACKGROUND: The clinical manifestations of group A streptococcus (GAS) (Streptococcus pyogenes) are diverse, ranging from asymptomatic colonization to devastating invasive disease. Maternity-related clusters of invasive GAS (iGAS) infection are complex to investigate and control, especially if recurrent. AIM: To investigate three episodes of emm 75 GAS/iGAS infection in maternity patients at one hospital site over a four-year period (two with monophyletic ancestry). METHODS: The episodes are described, together with whole-genome sequence (WGS) isolate analyses. Single nucleotide polymorphism differences were compared with contemporaneous emm 75 genomes. FINDINGS: Over the four-year study period, seven mothers had emm 75 GAS/iGAS and one mother had emm 3 iGAS (in year 4) (subsequently discounted as linked). Three (clinical/screening samples) of the seven babies of emm-75-positive mothers and three screened healthcare workers were positive for emm 75 GAS. WGS similarity suggested a shared ancestral lineage and a common source transmission, but directionality of transmission cannot be inferred. However, the findings indicate that persistence of a particular clone in a given setting may be long term. CONCLUSIONS: Occupational health procedures were enhanced, staff were screened, and antibiotic therapy was provided to GAS-positive staff and patients. The definitive source of infection could not be identified, although staff-patient transmission was the most likely route. The pattern of clonal GAS transmission over the four-year study period suggests that long-term persistence of GAS may have occurred.

The influence of previous exposure to environmental mycobacteria on the interferon-gamma response to bacille Calmette-Guérin vaccination in southern England and northern Malawi.

We report a large study of the effect of BCG vaccination on the in vitro 6-day whole blood interferon-gamma (IFN-gamma) response to antigens from eight species of mycobacteria among schoolchildren in south-eastern England, where bacille Calmette-Guérin (BCG) vaccination is highly protective against pulmonary tuberculosis, and among young adults in northern Malawi, where BCG vaccination is not protective. In the UK children, BCG induced an appreciable increase in IFN-gamma response to antigens from most species of mycobacteria. The degree of change was linked to the relatedness of the species to Mycobacterium bovis BCG, and provides further evidence of the cross-reactivity of mycobacterial species in priming of the immune system. IFN-gamma responses to purified protein derivatives (PPDs) from M. tuberculosis and environmental mycobacteria were more prevalent in the Malawian than the UK group prior to vaccination; BCG vaccination increased the prevalence of responses to these PPDs in the UK group to a level similar to that in Malawi. There was no evidence that the vaccine-induced change in IFN-gamma response was dependent upon the magnitude of the initial response of the individual to environmental mycobacteria in the United Kingdom or in Malawi. These observations should assist the development and interpretation of human clinical trials of new vaccines against M. tuberculosis in areas of both low and high exposure to environmental mycobacteria.

Interferon-gamma and skin test responses of schoolchildren in southeast England to purified protein derivatives from Mycobacterium tuberculosis and other species of mycobacteria.

The immune responses of schoolchildren in southeast England to Mycobacterium tuberculosis and other species of mycobacteria were studied prior to vaccination with bacille Calmette-Guérin (BCG). Data are presented for tuberculin (Heaf) skin test and interferon-gamma (IFN-gamma) responses to M. tuberculosis purified protein derivative (PPD), and IFN-gamma responses to PPDs from eight other environmental mycobacteria, measured in 424 schoolchildren (13-15 years of age). Responses to M. tuberculosis PPD were detected in 27% of schoolchildren by in vitro IFN-gamma response and in 20% by the Heaf test. IFN-gamma responses were more prevalent to PPDs from species of mycobacteria other than M. tuberculosis, predominantly those of the MAIS complex and M. marinum (45-60% responders). Heaf test and IFN-gamma responses were associated (P<0.001) for M. tuberculosis, MAIS and M. marinum. These findings have implications for appropriate implementation of vaccination against tuberculosis.

Oral ciprofloxacin plus colistin: prophylaxis against bacterial infection in neutropenic patients. A strategy for the prevention of emergence of antimicrobial resistance.

Following a 2-year study, the combination of oral ciprofloxacin and colistin has been used continuously for 10 years without the emergence of resistance. During a 2-year period (1987-1989), we compared ciprofloxacin + colistin (CIP + COL) with neomycin + colistin (NEO + COL) in a randomized trial--combinations chosen because of the potential for prophylaxis of Gram-negative infection by ciprofloxacin, with colistin given to reduce the risk of emergence of resistance. Sixty-four patients with similar demographics in each arm were evaluable for efficacy analysis. Patients on CIP + COL had a significantly lower proportion of neutropenic days with fever (P < 0.001) and neutropenic days on intravenous antibiotics (P < 0.001) than patients on NEO + COL. A total of 54 (15 bacteriologically documented) pyrexial episodes occurred in patients on CIP + COL and 77 (41 bacteriologically documented) in patients on NEO + COL. Only two Gram-negative bacterial infections occurred in the CIP + COL arm compared with 16 in the NEO + COL arm. No Staphylococcus aureus infections occurred in the CIP + COL group compared with 10 in the other patients. Two CIP-resistant Gram-negative bacilli were isolated from patients on CIP + COL compared with 13 NEO-resistant Gram-negative bacilli from patients on NEO + COL. Following a subsequent decade of unchanged use of this prophylactic strategy in neutropenic patients, a 2-year follow-up study between 1 January 1998 and 31 December 1999 showed 66 significant infections during 700 [corrected] neutropenic episodes. Thirty-five of the 111 (31%) isolates were ciprofloxacin-resistant, involving 5% of the neutropenic episodes [corrected].

Contamination of allotment soil with lead: managing potential risks to health.

BACKGROUND: In the context of contaminated land, assessing risk involves identifying a source, a pathway and a receptor. We describe how this approach worked in practice following the discovery of high lead levels in the soil of an allotment site in a London borough. METHODS: Soil and produce analyses were undertaken. A worst-case scenario was constructed to estimate the maximum potential lead intake by consumers. A questionnaire survey was undertaken of individuals who either worked on the allotment or ate significant amounts of produce grown on it. They were also offered blood lead tests. RESULTS: High lead levels were found in soil and produce. The worst-case assessment showed that the estimated lead intake by a hypothetical consumer of allotment produce exceeded the provisional tolerable weekly intake almost 10-fold. Further tests on produce indicated that soil contamination had contributed to the high lead levels. The questionnaire survey did not reveal any chronic illness related to lead exposure. Of the five tested, none had raised blood lead levels. CONCLUSIONS: A decision was made to remediate the site. Pending this, we advised the allotment holders not to cultivate the land or eat any produce grown on it as we could not be sure that preparation of the produce before consumption would remove all adherent lead-contaminated soil, and continued cultivation could also expose them to lead in the soil dust.

Are HIV lookbacks worthwhile? Outcome of an exercise to notify patients treated by an HIV infected health care worker. Incident Management Teams.

This report describes the management and outcome of one of the largest exercises undertaken in the United Kingdom to notify patients exposed to an HIV infected health care worker. Eighty-six per cent (1597/1852) of patients on whom the infected junior doctor in obstetrics and gynaecology had performed surgical procedures were contacted and 1180 women (64% of those exposed) elected to be tested. None was found to be positive. Of those tested, 651 had undergone procedures classified as 'higher risk' and 529 'low risk' procedures. These data provide further evidence that the overall risk of transmission from an infected health care worker to patients is likely to be very low. HIV lookbacks may be worthwhile but we consider that it would be justifiable to notify and offer HIV testing only to patients who have undergone higher risk procedures. The estimated cost to the NHS of this exercise exceeded 200,000 Pounds.

Surveillance of waterborne disease in England and Wales.

A pilot scheme, designed to improve the information on waterborne disease available nationally, was set up in five health regions from October 1991 to March 1992. Consultants in communicable disease control were asked to report each month on confirmed and suspected cases of waterborne disease, and microbiological and other contamination incidents. Twelve events were reported to the PHLS Communicable Disease Surveillance Centre (CDSC) in six months: five involved human illness and seven were contamination incidents. Six other events were reported to CDSC from regions that did not take part in the scheme. The total number of events reported was small and epidemiological evidence that linked disease with water consumption was often weak or absent. Nevertheless, the scheme provided valuable information on events associated with water and would prove useful if it were established nationally, linked with guidance on the investigation of incidents.

The inappropriate use of acute hospital beds in an inner London District Health Authority.

The requirement for District Health Authorities to assess the health care needs of their population implies that they must consider how well acute hospital care meets these identified needs. This study, which was conducted in an inner London health district, identified that 123 (14.6%) patients were perceived by medical and/or nursing staff to be inappropriately located in an acute bed. This group was dominated by patients aged 65 years or above, those in general and geriatric medicine, those with a length of stay of 30 days or more, and those with high levels of physical and mental dependency. The main reasons for patients being labelled as 'inappropriate' were the need for non-acute health services (eg rehabilitation, terminal care etc), a need for nursing home places or because of social or housing problems. Five months after identification, the notes of 100 of the 123 inappropriate patients were traced. Retrospective classification of these notes using the more 'objective' Oxford Bed Study Instrument showed that 97 patients were still defined as inappropriate. Details of the length of inappropriate stay were available for 74 patients who accrued 7,519 inappropriate bed days at a cost of 836,547 pounds. These patients are an illustration of the potential failings of current health and social care systems and highlight the need for imaginative care solutions which bridge this divide.

A survey of invasive Haemophilus influenzae infections.

A survey of invasive H. influenzae infections has been underway in six regions of England and Wales since September 1990. In the first year, there were 433 cases of which 362 (84%) were due to H. influenzae type b (Hib). The majority of Hib infections were in children aged less than 5 years; there being an annual incidence of 26.4/100,000 in this age group. Meningitis occurred in 56% of cases of Hib infection. The results confirm previous evidence of the need to incorporate Hib vaccination into the childhood immunisation schedule. The ongoing survey data will provide useful information to assess the impact of an Hib immunisation programme.

A prospective randomised comparison of cefotaxime vs. netilmicin vs. cefotaxime plus netilmicin in the treatment of hospitalised patients with serious sepsis.

93 patients were enrolled into a prospective randomised study to determine the efficacy and safety of netilmicin, cefotaxime or their combination in the treatment of sepsis caused by susceptible strains of Enterobacteriaceae or staphylococci. 83 patients were evaluable for safety, 74 for clinical efficacy and 63 for microbiological response including 36 patients (57%) with positive blood cultures. There were significantly more clinical failures with cefotaxime than with netilmicin even when urinary tract sepsis was excluded. Microbiological failures occurred more frequently in the cefotaxime arm and were associated with Klebsiella and Enterobacter spp. Four cefotaxime failures were subsequently successfully treated with netilmicin. More mixed infections were however enrolled by chance into the cefotaxime arm. The statistical difference between netilmicin and cefotaxime is not significant if mixed infections are excluded. There was no difference in efficacy between the netilmicin and combination groups although superinfection was seen in the latter group. The incidence of nephrotoxicity was greater in the netilmicin group but not significantly so. Only one minor case of ototoxicity was detected in the 41 patients receiving netilmicin who had serial audiograms. The results suggest that netilmicin is a more effective agent than cefotaxime for treating life-threatening infections with susceptible Enterobacteriaceae or staphylococci particularly with infections in non-urinary tract sites. If dosage of netilmicin is closely monitored by measuring serum concentrations, toxicity is minimal.