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Biomedical subjects

D Cubitt

Publications and source records attributed to D Cubitt.

At least 19 recordsLinked to original sources
PubMed2005

Improved outcome for children with disseminated adenoviral infection following allogeneic stem cell transplantation.

Adenovirus (AdV) infections are a frequent cause of morbidity and mortality following allogeneic stem cell transplantation (SCT), and disseminated infection is associated with high mortality, particularly in paediatric SCT. Here, we describe an approach to reduce mortality from adenoviraemia by combining prospective monitoring for the occurrence of adenoviraemia using a sensitive polymerase chain reaction method, early antiviral therapy and prompt withdrawal of immunosuppression. A total of 155 consecutive paediatric SCT procedures were prospectively monitored, of which 113 (73%) transplants involved donors other than matched siblings and 126 (83%) employed T-cell depletion. Adenoviraemia was detected in 26/155 (17%) transplants and developed exclusively in patients who had received T-cell-depleted grafts. Withdrawal of immunosuppression coupled with early antiviral therapy led to resolution of adenoviraemia in 19/26 (81%) patients with only five patients succumbing to disseminate AdV infection. Survival from adenoviraemia was associated with lymphocyte recovery to above 0.3x10(9)/l. Mortality was closely linked with the absence of lymphocyte recovery because of profound T-cell depletion of the graft with CD34+ magnetic-activated cell sorting. Mortality from disseminated AdV infection was 5/26 (19%) in this study, which is significantly lower than previously reported.

Adenoviridae↗
PubMed2004

Enterovirus myocarditis as a cause of neonatal collapse.

Seven neonates required intensive care at our institution with enterovirus myocarditis, 2001-2003. Presentation was at a median age of 9 days. All had ischaemic electrocardiograms, poor ventricular function, raised creatine kinase, and enterovirus RNA detected by reverse transcriptase polymerase chain reaction. Four survived. Enterovirus myocarditis may be an under recognised cause of neonatal collapse.

Electrocardiography↗
PubMed2002

Epstein-Barr virus monitoring in paediatric renal transplant recipients.

Prospective Epstein-Barr virus (EBV) surveillance post transplant was undertaken by qualitative polymerase chain reaction testing for EBV DNA in plasma so as to detect EBV viremia as early as possible and thereby attempt to pre-empt post-transplant lymphoproliferative disease by reduction of immunosuppression. Forty-three children (46 transplants) were followed for a median (range) of 15.5 (3-25) months. Thirty-one children (67%) were EBV seropositive pre transplant. Twenty children (44%) developed EBV viremia; of these 9 (60%) were seronegative and 11 (36%) seropositive recipients. Primary infection developed later (median difference 14.2 weeks, P=0.009), was more likely to be symptomatic (odds ratio 2.91, 95% confidence interval 0.95-4.88) and associated with a rise in serum creatinine (odds ratio 6.13, 95% confidence interval 4.13-8.13) than reactivation disease. There was a higher incidence of EBV disease in children receiving quadruple therapy and tacrolimus (odds ratio 13.2, 95% confidence interval 11.5-14.9) compared with those given cyclosporin-based immunosuppression. Immunosuppression was reduced when EBV infection was detected. All children became asymptomatic and renal function returned to normal by a median (range) of 17 (6-52) days, although mild relapses occurred in 3 children. Regular EBV surveillance allowed prompt reduction of immunosuppression and was associated with a good outcome in this group of children.

Adolescent↗
PubMed2002

Faecal elastase 1 concentration is a marker of duodenal enteropathy.

BACKGROUND: Measurement of faecal elastase (FE1) is used widely to screen for pancreatic exocrine insufficiency (PI). FE1 does not allow differentiation of primary from secondary PI. AIMS: To investigate the relation between duodenal morphology and FE1 in children with secondary PI resulting from primary gastrointestinal diseases. METHODS: A group of 51 children underwent small intestinal biopsy and FE1 measurement. Villus to crypt ratio (VCR) and inflammation within the lamina propria of duodenal mucosal biopsy specimens were scored and compared with FE1 values. RESULTS: In 51 children from nine diagnostic categories, a highly significant correlation between FE1 and both duodenal morphology and inflammation was found. CONCLUSION: Small bowel enteropathy is associated with low FE1 concentrations, indicative of secondary exocrine pancreatic insufficiency.

Biomarkers↗
PubMed2001

Amino acid substitution within the VP7 protein of G2 rotavirus strains associated with failure to serotype.

Rotavirus strains collected in the United Kingdom during the 1995-1996 season and genotyped as G2 by reverse transcription-PCR failed to serotype in enzyme-linked immunosorbent assays using three different G2-specific monoclonal antibodies. The deduced amino acid sequences of the antigenic regions A (amino acids 87 to 101), B (amino acids 142 to 152), and C (amino acids 208 to 221) of VP7 revealed that a substitution at position 96 (Asp-->Asn) correlated with the change in ability to serotype these G2 strains.

Amino Acid Sequence↗
PubMed2000

Characterisation of rotavirus G9 strains isolated in the UK between 1995 and 1998.

G9P[6] and G9P[8] rotavirus strains were identified during 1995/96 through the molecular epidemiological surveillance of rotavirus strains circulating in the UK between 1995 and 1998. An increase in the incidence and spread of sporadic infections with rotavirus genotype G9P[8] across the UK was detected in the two following seasons. Partial sequencing of the VP7 gene showed that all the UK strains shared a high degree of homology and were related very closely to G9 strains from the US and from symptomatic infections in India (> or =96% homology). The UK strains were related more distantly to the apathogenic Indian strain 116E (85-87.8% homology). Phylogenetic analysis revealed clustering of the UK strains into 3 different lineages (I to III) and into two sub-lineages within lineage I. There were correlations between VP7 sequence clustering, the P type and the geographical origin of the G9 strains. Partial sequencing of the VP4 gene showed high degree of homology (>98%) among all the P[6] strains, and the sequences obtained from the P[8] strains clustered into 2 of the 3 global lineages described for P[8] strains associated with other G types. These data suggest that G9 strains may be a recent importation into the UK, and that G9P[8] strains may have emerged through reassortment in humans between G9P[6] strains introduced recently and the more prevalent cocirculating G1, G3 and G4 strains that normally carry VP4 genes of P[8] type.

Aged↗
PubMed1999

Effect of the worldwide epidemic on HIV prevalence in the United Kingdom: record linkage in anonymous neonatal seroprevalence surveys.

OBJECTIVE: To assess the impact of the worldwide HIV/AIDS epidemic on the prevalence of HIV in women in the United Kingdom (UK), particularly in the large immigrant and ethnic minority communities. METHOD: Unlinked anonymous neonatal seroprevalence survey with electronic record linkage of data from child health computers (maternal age and ethnic status) and birth registration (parent's country of birth). RESULTS: Of a total 137456 samples collected in 1997-1998, 188 (0.14%) were anti-HIV-1 seropositive. Seroprevalence was highest in women born in East Africa (2.3%) and Central Africa (1.9%). 76.4% of seropositive newborns were delivered to mothers born in sub-Saharan Africa; a further 6.0% had fathers from sub-Saharan Africa. However, there was little evidence of HIV in women born in Southern Asia [prevalence 0.0081%; 95% confidence interval (CI) 0-0.04], and none within UK-born Asian communities. Prevalence among the UK-born Black African community was low (0.14%; 95% CI 0-0.6). Among infants with both parents known to be born in the UK, seroprevalence was 0.023% (95% CI 0.01-0.04) in London, and zero (95% CI 0-0.007) in non-Metropolitan areas. Irrespective of mother's region of birth, seroprevalence was 4.2 times higher (95% CI 3.0-5.8) in newborns whose father's details were not recorded at birth registration, a marker for single unsupported mothers. CONCLUSION: The risk of HIV among pregnant women from sub-Saharan Africa has been recognized. However, in southern England, HIV is very rare in women from Southern Asia and in UK-born women in ethnic minority communities, in spite of cultural and travel ties to high-prevalence countries. Data linkage in anonymous surveys assists in monitoring the impact of the worldwide epidemic on prevalence and incidence locally.

Adult↗
PubMed1995

Development of an ELISA to detect MX virus, a human calicivirus in the snow Mountain agent genogroup.

MX virus is a Snow Mountain agent (SMA) genogroup human calicivirus (HuCV) identified in a Mexican child with diarrhoea. An ELISA using hyperimmune antisera to the recombinant MX virus (rMX) capsid was developed to detect SMA genogroup HuCVs in stool specimens. The rMX ELISA detected the prototype MX virus, SMA, and Hawaii agent (HA), but not Norwalk virus (NV) or Sapporo virus. Twenty-three diarrhoea stool specimens from children attending day care centres in Norfolk, Virginia, were positive by the rMX ELISA and results were confirmed by reverse transcription-polymerase chain reaction (RT-PCR). Eight of 20 diarrhoea stool specimens from children in the United Kingdom previously shown to contain small round structured viruses (SRSVs) or HuCVs by electron microscopy were also positive by the rMX ELISA and RT-PCR. Sequence analysis of the RT-PCR products showed that all the rMX ELISA-positive viruses belong to the SMA genogroup. These data also showed that the SMA genogroup can be further divided into two subgroups: subgroup 1 includes prototypes SMA and HA, and subgroup 2 includes MX virus, minireovirus, Oth-25 and Bristol virus.

Animals↗
PubMed1994

Identification of astrovirus serotypes from children treated at the Hospitals for Sick Children, London 1981-93.

An enzyme immunoassay (EIA) for astrovirus type 1 together with immune electronmicroscopy (IEM) was used to type a collection of 162 astroviruses obtained from 1981-93 from children with diarrhoea. The EIA was found to be specific for astrovirus type 1. Astrovirus types 2-4 were typed by IEM. Astrovirus type 1 was the prevalent serotype 107/125 (86%), followed by type 3 (8%), type 4 (6%) and type 2 (1%). Six samples containing astrovirus could not be typed or detected by EIA because they were coated with coproantibodies; 11 others were not identified. Virus particles could no longer be detected in 15/162 (9%) samples following storage for > or = 2 years. Selected samples containing astrovirus types 1-4 were passaged in CaCO2 cells and their identity confirmed by one or both assays. One sample was shown to have remained viable for 10 years when stored as an aqueous suspension at -20 degrees C. Two patients with severe combined immune deficiency disease (SCID) were shown to be excreting astrovirus type 1 for 32 and 102 days respectively. One child was simultaneously shedding rotavirus and the other child was excreting adenovirus.

Child↗
PubMed1994

Use of anonymous newborn serosurveys to evaluate antenatal HIV screening programmes.

OBJECTIVE: To evaluate the extent to which antenatal HIV screening programmes identify HIV infected women who go to term. DESIGN: Comparison of results of two surveillance systems. An anonymous neonatal HIV serosurvey was used to estimate the numbers of HIV infected women giving birth; reporting by obstetricians was used to assess the proportion who had been identified. SETTING: Three Thames regions. RESULTS: 729,105 neonatal blood samples were tested, of which 484 were HIV seropositive. Newborn HIV seroprevalence is increasing, at different rates, in inner London, suburban London, and in non-metropolitan districts. During the past four years the proportion of infected women who have been identified before delivery is 16.9%, but less than half of these were diagnosed during pregnancy. In 1993 only five of the 128 (4%) previously undiagnosed infected women delivering babies were identified by antenatal screening. CONCLUSION: Despite increased emphasis on antenatal testing for HIV in areas of higher prevalence the number of undiagnosed women delivering babies continues to increase. Consideration should be given to alternative strategies for offering antenatal HIV testing. Antenatal screening programmes should be monitored continuously by comparing anonymous neonatal seroprevalence with clinical reports from obstetricians.

Confidence Intervals↗
PubMed1993

Efficacy of a recombinant Norwalk virus protein enzyme immunoassay for the diagnosis of infections with Norwalk virus and other human "candidate" caliciviruses.

A recombinant Norwalk virus antigen enzyme immunoassay (rNV EIA) for the detection fo Norwalk virus (NV) antibodies was evaluated using sera from volunteers and patients infected with Norwalk, Hawaii, Snow Mountain Agent, small round structured viruses (SRSV), and human calicivirus (HuCV) strains. The results for NV antibodies correlated well with previous results obtained using a NV radioimmunoassay. The test rNV EIA was found to be highly specific for NV. The results of tests on sera obtained from patients involved in confirmed outbreaks of SRSV in the UK showed that only 1/12 was due to Norwalk virus. Further evidence is presented that SRSV strain UK2 is antigenically related to NV.

Adult↗
PubMed1993

Maternal prevalence of Toxoplasma antibody based on anonymous neonatal serosurvey: a geographical analysis.

A total of 12,902 neonatal samples collected on absorbent paper for routine metabolic screening were tested anonymously for antibodies to toxoplasma. Seroprevalence varied from 19.5% in inner London, to 11.6% in suburban London, and 7.6% in non-metropolitan districts. Much of this variation appeared to be associated with the proportions of livebirths in each district to women born outside the UK. However, additional geographical variation remained and seroprevalence in UK-born women was estimated to be 12.7% in inner London, 7.5% in suburban London, and 5.5% in non-metropolitan areas. These estimates are considerably lower than any previously reported in antenatal sera in the UK. The wide geographical variation highlights a need for further research to determine the relative importance of different routes of transmission.

Antibodies, Protozoan↗
PubMed1992

Two methods for assessing the risk-factor composition of the HIV-1 epidemic in heterosexual women: southeast England, 1988-1991.

OBJECTIVE: The prevalence of HIV-1 in the heterosexual population in southeast England between 1988 and 1991 was examined using two methods. DESIGN AND METHODS: First, district neonatal seroprevalence was compared on a geographical basis to social and demographic variables reflecting risk-factor prevalence. Second, over the same period eight children who developed AIDS within the first 12 months of life were born. RESULTS: The differences in seroprevalence between districts could be explained by the proportion of livebirths to women born in parts of Africa. An estimated 92% of neonatal seropositives could be associated with this demographic variable. The proportions of livebirths to women born in other countries, the prevalence of notified injecting drug use, and area measures of social deprivation, were only poorly related to HIV seroprevalence, and had no additional explanatory value. Seven of the eight (87.5%) children who developed AIDS in the first year were born to black women from Africa. CONCLUSIONS: Both methods suggest that a high proportion of heterosexually transmitted HIV in southeast England has been imported.

Adult↗
PubMed1991

Prevalence of maternal HIV-1 infection in Thames regions: results from anonymous unlinked neonatal testing.

To monitor the spread of human immunodeficiency virus (HIV) in the heterosexual population, residues of blood samples collected routinely on absorbent paper for neonatal screening (Guthrie cards) in NE, NW, and SW Thames Regions in England have been tested for antibodies to HIV-1 since June, 1988. 323,369 dried blood spots were analysed to end March, 1991. Prevalence of anti-HIV-1 in newborn babies has remained stable in outer London and non-metropolitan districts whereas prevalence in inner London has increased from 1 in 2000 in the 12 months beginning June, 1988, to 1 in 500 in the first 3 months of 1991. Either exponential or linear growth in the numbers of new seropositives could account for the results. That obstetricians were aware of maternal HIV infection in only 20% of infected pregnancies, indicates the extent to which HIV infection goes unrecognised in the heterosexual community.

Confidentiality↗