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C Anthony Hart

Publications and source records attributed to C Anthony Hart.

At least 73 records · Page 4Linked to original sources
PubMed2003

Anaplasma phagocytophilum reduces neutrophil apoptosis in vivo.

Ovine neutrophils spontaneously underwent apoptosis during culture in vitro, as assessed by morphological changes and exposure of annexin V binding sites on their cell surfaces. The addition of conditioned medium from concanavalin A-treated ovine peripheral blood mononuclear cells (PBMC) could partially protect against this progression into apoptosis, but dexamethasone and sodium butyrate could not. Actinomycin D accelerated the rate at which ovine neutrophils underwent apoptosis. Neutrophils isolated from sheep experimentally infected with Anaplasma phagocytophilum showed significantly delayed apoptosis during culture ex vivo, and the addition of conditioned medium from PBMC to these cells could not delay apoptosis above the protective effects observed after in vivo infection. The ability of neutrophils from A. phagocytophilum-infected sheep to activate a respiratory burst was increased compared to the activity measured in neutrophils from uninfected sheep, but chemotaxis was decreased in neutrophils from infected sheep. These data are the first demonstration that in vivo infection with A. phagocytophilum results in changes in rates of apoptosis of infected immune cells. This may help explain how these bacteria replicate in these normally short-lived cells.

Anaplasma phagocytophilum↗
PubMed2003

Molecular analysis of the 18S rRNA gene of Cryptosporidium parasites from patients with or without human immunodeficiency virus infections living in Kenya, Malawi, Brazil, the United Kingdom, and Vietnam.

An 840-bp fragment of the 18S rRNA gene was used to identify Cryptosporidium spp. recovered from human immunodeficiency virus (HIV)-infected and -uninfected patients from Kenya, Malawi, Brazil, the United Kingdom, and Vietnam. Initial identification was by Ziehl-Neelsen acid-fast staining. Confirmation was by nested PCR, targeting the most polymorphic region of the 18S rRNA gene. Genotyping was by restriction endonuclease digestion of the PCR product followed by nucleotide sequencing. Among 63 isolates analyzed, four genotypes of Cryptosporidium were identified; 75% of the isolates were of the C. parvum human genotype, while the potentially zoonotic species were of the C. parvum bovine genotype (21.7%), the C. meleagridis genotype (1.6% [one isolate]), and the C. muris genotype (1.6% [one case]). HIV-infected individuals were more likely to have zoonotic genotypes than the HIV-uninfected individuals. Among the C. parvum group, strains clustered distinctly into either human or bovine genotypes regardless of the geographical origin, age, or HIV status of the patients. The intragenotypic variation observed in the C. parvum human genotype was extensive compared to that within the C. parvum bovine genotype group. The variation within genotypes was conserved in all geographical regions regardless of the patients' HIV status. The extensive diversity within genotypes at the 18S rRNA gene locus may limit its application to phylogenetic analyses.

AIDS-Related Opportunistic Infections↗
PubMed2003

Molecular typing of, and distribution of genetic markers among, Burkholderia cepacia complex isolates from Brazil.

PCR tests were used to assign genomovar status to 39 non-cystic fibrosis (non-CF) and 11 CF Burkholderia cepacia complex isolates from patients in hospitals in Recife, Brazil. Non-CF isolates were assigned to genomovar IIIA (71.8%), genomovar I (15.4%), B. vietnamiensis (7.7%), and B. multivorans (5.1%). CF isolates were assigned to genomovar IIIA (18.2%), B. vietnamiensis (18.2%), and genomovar I (9.1%). Six CF isolates sharing recA PCR-restriction fragment length polymorphism (RFLP) and randomly amplified polymorphic DNA (RAPD) patterns could not be assigned to a genomovar. 16S rDNA sequence obtained from these isolates indicated a closest relationship to B. anthina, but the recA sequence was equally divergent from several genomovars. PCR screening indicated the presence of cblA in only two isolates, whereas the B. cepacia epidemic strain marker was found in 22 of 28 genomovar IIIA isolates. A type III secretion gene was detected in all but genomovar I isolates. RAPD and PCR-RFLP assays, targeting both recA and fliC, indicated a large amount of genetic variability among the isolates, with many novel patterns being observed. Nine genomovar IIIA isolates from different non-CF patients and clinical sources had identical genotypes, indicating the presence of a common clone.

Bacterial Typing Techniques↗
PubMed2003

Zinc supplementation in Brazilian children with acute diarrhoea.

Although oral rehydration therapy greatly reduces mortality from diarrhoeal diseases, it has little effect on stool frequency. However, there is mounting evidence that zinc is an effective adjunct to the treatment of diarrhoea, although few studies have examined its efficacy in Latin America. This study assessed the efficacy of zinc supplementation in children with acute diarrhoea in Brazil. The study was a double-blind, placebo-controlled, randomised, clinical trial in children <5 years of age attending emergency services in Sergipe, Brazil. Subjects received zinc or vitamin C as placebo. There was a marked reduction in the duration of the diarrhoea (1.1 vs 2.6 days) and of watery stools in the zinc-supplemented group. The efficacy of zinc was independent of the presence of viral enteropathogens in the stools. It is concluded that, similar to studies in India and Bangladesh, zinc could be an important adjunct for treating acute diarrhoea in Brazilian children.

Acute Disease↗
PubMed2003

Human metapneumovirus in severe respiratory syncytial virus bronchiolitis.

Reverse transcription-polymerase chain reaction was used to detect segments of the M (matrix), N (nucleoprotein), and F (fusion) genes of human metapneumovirus in bronchoalveolar fluid from 30 infants with severe respiratory syncytial virus bronchiolitis. Seventy percent of them were coinfected with metapneumovirus. Such coinfection might be a factor influencing the severity of bronchiolitis.

Bronchiolitis, Viral↗
PubMed2003

Human metapneumovirus and respiratory syncytial virus, Brazil.

We describe the epidemiologic and clinical characteristics of 111 children attending clinics and hospitals in Aracaju, northeast Brazil, with acute respiratory infections attributable to human metapneumovirus (HMPV), respiratory syncytial virus (RSV), or both in May and June 2002. Fifty-three (48%) children were infected with RSV alone, 19 (17%) with HMPV alone, and 8 (7%) had RSV/HMPV co-infections.

Brazil↗
PubMed2003

IgA antibodies to human immunodeficiency virus in serum, saliva and urine for early diagnosis of immunodeficiency virus infection in Ugandan infants.

The value of HIV-1 IgA antibodies for early diagnosis of HIV infection in infants in serum, saliva and urine was investigated at Mulago Hospital, Kampala. Sensitivity and specificity in serum of HIV-infected infants at different ages were: 0 to 1 months, 88 and 95%; 1 to 3 months, 88 and 97%; 4 to 6 months, 80 and 96%. They decreased between 67 and 77% and 80 to 91%, respectively, in older age groups. Sensitivity for saliva was lower (53 to 79%) and urine only 37 to 62%, although specificity was reasonably high (>85%). The high proportion of infants with raised HIV IgA in the first months of life (88%) may represent prenatal infection. Sensitivity of serum and especially salivary and urinary HIV IgA is too low to be of practical value for early diagnosis of HIV infection in infants.

Adult↗
PubMed2002

Prospective validation of the Glasgow Meningococcal Septicaemia Prognostic Score. Comparison with other scoring methods.

UNLABELLED: A prospective observational study was done to derive performance characteristics for the Glasgow Meningococcal Septicaemia Prognostic Score (GMSPS) and compare it with nine other severity scores (Stokland, Stiehm and Damrosch, Ansari, Niklasson, Leclerc, Kahn and Blum, Lewis, Istanbul and Bjark) and laboratory markers of disease severity. In the paediatric departments of six hospitals in Merseyside, UK, 278 children with confirmed or probable meningococcal disease were admitted between November 1988 and August 1990 ( n=152) and between September 1992 and April 1994 ( n=126); 26 of whom died. GMSPS was recorded on admission and again if there was clinical deterioration. Laboratory markers of disease severity (including endotoxin and cytokine levels) were measured on admission. The nine other scores were recorded on the first cohort. "Maximum" GMSPS (before referral to the paediatric intensive care unit) was achieved within 12 h of arrival in 97% of children. A GMSPS > or =8 had sensitivity 100%, specificity 75% and positive predictive value for death of 29%, GMSPS > or =10 had 100%, 88% and 46% respectively. All 26 who died scored >10, before referral to the paediatric intensive care unit. GMSPSs calculated by other medical staff had similar characteristics to those calculated by research fellows. All scores correlated significantly with white cell count, coagulopathy, endotoxin and cytokine levels. However, the predominantly clinical scores were the most robust. GMSPS had amongst the best performance characteristics of all scores and was more sensitive than laboratory markers. CONCLUSION: the Glasgow Meningococcal Septicaemia Prognostic Score is an easily performed, repeatable, clinical score that can rapidly identify children with fulminant meningococcal disease. When performed prospectively, a score > or =8 had a positive predictive value for death of 29%. This score can identify those children who should be offered intensive care and can select those who may benefit from novel therapies.

Biomarkers↗
PubMed2002

Non-typhoidal salmonella bacteraemia among HIV-infected Malawian adults: high mortality and frequent recrudescence.

OBJECTIVE: Non-typhoidal salmonella (NTS) bacteraemia is a common, recurrent illness in HIV-infected African adults. We aimed to describe the presentation and outcome of NTS bacteraemia, the pattern of recurrence, and to determine whether recurrence results from re-infection or recrudescence. DESIGN: One hundred consecutive adult inpatients with NTS bacteraemia in Blantyre, Malawi, were treated with chloramphenicol. Survivors were prospectively followed to detect bacteraemic recurrence. METHODS: Index and recurrent isolates were typed by antibiogram, pulsed-field gel electrophoresis and plasmid analysis to distinguish recrudescence from re-infection. RESULTS: Inpatient mortality was 47%, and 1-year mortality was 77%. A total of 77 out of 78 cases were HIV positive. Anaemia was associated with inpatient death, and several features of AIDS were associated with poor outpatient survival. Among survivors, 43% (19/44) had a first recurrence of NTS bacteraemia at 23-186 days. Among these, 26% (5/19) developed multiple recurrences up to 245 days. No recurrence was seen after 245 days, despite follow-up for up to 609 days (median 214). Suppurative infections were not found at presentation, and were only seen twice at recurrence. Index and recurrent paired isolates were identical by phenotyping and genotyping, consistent with recrudescence, rather than re-infection. CONCLUSION: NTS bacteraemia has a high mortality (47%) and recurrence (43%) rate in HIV-infected African adults. Recurrence is caused by recrudescence rather than re-infection. As focal infections were rarely found, recrudescence may often be a consequence of intracellular tissue sequestration. There is an urgent need for improved primary treatment and secondary prophylaxis in Africa.

Adult↗
PubMed2002

Lack of clonal relationship between non-typhi Salmonella strain types from humans and those isolated from animals living in close contact.

Antibiogram patterns and chromosomal DNA typing were used to compare 151 non-typhoidal Salmonella spp. (NTS) isolated from patients and 78 from animals, environmental or food specimens obtained within or near the homes of patients with invasive salmonellosis. The majority of NTS from humans (137; 90.7%) were Salmonella enterica serotype Typhimurium (S. Typhimurium) and S. Enteritidis. Chicken specimens and feeds produced (24; 52.2%) S. Enteritidis, while S. Agona was the predominant (20; 77%) serovar among pigs and dairy cows. The majority (97; 64.2%) of NTS from humans were multidrug resistant, while NTS from cows, pigs, beef carcass swabs and sewers were fully susceptible to all antibiotics tested. Pulsed-field gel electrophoresis patterns of XbaI-digested genomic DNA of NTS from the humans and the chickens were different. However, S. Enteritidis from chickens, and S. Braenderup and S. Agona from cows and pigs were clustered together in one group. There was no significant relatedness between NTS isolates from humans and those from animals, food or the environment in close contact to humans.

Animals↗
PubMed2002

Detection and characterisation of human astroviruses in children with acute gastroenteritis in Blantyre, Malawi.

In a 2-year hospital-based study of paediatric gastroenteritis in Blantyre, Malawi, astroviruses were detected by enzyme immunoassay in 15 (1.9%) of 786 inpatients and in 9 (2.3%) of 400 outpatients. Greater disease severity was noted in children coinfected with human immunodeficiency virus (HIV). Six human astrovirus (HAstV) genotypes were identified, including HAstV-1 (25%), HAstV-2 (21%), HAstV-3 (25%), HAstV-4 (13%), HAstV-5 (4%), and HAstV-8 (13%). Although astroviruses are not major causes of gastroenteritis among children admitted to hospital in Blantyre, concomitant HIV infection appears to be a risk factor for increased severity of disease.

Acute Disease↗
PubMed2002

Respiratory syncytial virus bronchiolitis: disease severity, interleukin-8, and virus genotype.

In infants with respiratory syncytial virus (RSV) bronchiolitis, we investigated whether disease severity is associated with the genotype of the infecting virus, or with the infant's immunological response to the infection, as determined by measurement of interleukin-8 mRNA in the nasopharyngeal aspirate. This was a cross-sectional observational study, performed in the Accident and Emergency Department, wards, and Intensive Care Unit of a large pediatric hospital. Participants included 276 infants with respiratory syncytial virus infection. Outcome variables included: disease severity (infants requiring oxygen or ventilation were classified as having severe disease); RSV virus genotype (determined according to typing scheme based on the nucleoprotein and G glycoprotein genes); and amount of interleukin-8 mRNA in the nasopharyngeal aspirate, as measured by a semiquantitative polymerase chain reaction assay. This was corrected for the amount of cellular material in the sample by expressing it relative to mRNA for a constitutively expressed gene, HGPRT. We found a highly significant association between the ratio of interleukin-8 mRNA/HGPRT mRNA in the nasopharyngeal aspirate and the occurrence of severe disease. Odds ratio per unit increase of interleukin-8 mRNA/HGPRT mRNA was 1.15 (95% CI, 1.06, 1.24), P = 0.0004. There was no association between virus genotype and either disease severity or amount of interleukin-8 mRNA/HGPRT mRNA. In conclusion, there is a strong, dose-related association between interleukin-8 mRNA produced locally in the airways and disease severity, and a lack of association with virus genotype. This suggests that clinical manifestations of respiratory syncytial virus bronchiolitis are determined by local immunological responses to infection, rather than by characteristics of the infecting virus.

Bronchiolitis↗
PubMed2002

Cytokines in severe respiratory syncytial virus bronchiolitis.

Bronchiolitis caused by respiratory syncytial virus (RSV) infection is an important cause of severe lung disease in infants, and increasing evidence suggests that it is immunologically mediated. Experiments in mice suggest that this may be due to differential T-cell activation producing either type 1 or type 2 cytokines. We investigated this hypothesis in man by studying 24 infants ventilated with severe RSV bronchiolitis and by measuring messenger RNA (mRNA) for interleukin-4 (IL-4) and interferon-gamma (IFN-gamma), by polymerase chain reaction, in nasopharyngeal aspirates (NPAs) and bronchoalveolar lavage (BAL) fluids. A semiquantitative assay was used to estimate concentrations of mRNA for these cytokines in comparison to mRNA of the constitutively expressed hypoxanthine guanine phosphoribosyl transferase gene. BAL from 18/24 infants showed polarization of cytokine production: 6 with only IFN-gamma mRNA, and 12 with only IL-4 mRNA. For the 6/24 infants in whom both IL-4 mRNA and IFN-gamma mRNA were detected in BAL fluid, each was present in low amounts, compared with those with mRNA for IL-4 or IFN-gamma alone. IL-4 and IFN-gamma mRNA were not detected in any of the NPAs.These findings provide the first direct evidence in infants that in RSV bronchiolitis there are divergent T-cell responses and suggest that more than one mechanism may be responsible for immune-mediated disease enhancement.

Bronchiolitis↗
PubMed2002

Rotavirus vaccines: development, current issues and future prospects.

The potential benefit of safe and effective rotavirus vaccination in reducing morbidity and especially mortality from rotavirus gastroenteritis among children in developing countries has long been recognised. More recently, the focus of attention shifted to developed countries, where cost-effectiveness analyses justified the routine introduction of rotavirus vaccines into childhood immunisation schedules. The recent withdrawal in the U.S.A. of the first licensed rotavirus vaccine (the tetravalent rhesus reassortant rotavirus vaccine), following investigation into reports of intussusception among a number of vaccinees, has directed attention once more towards rotavirus vaccine use in developing countries. However, issues relating to vaccine safety, efficacy, and cost, remain to be overcome before widespread introduction of rotavirus vaccines can be anticipated.

Developing Countries↗
PubMed2002

Persistent and aggressive bacteria in the lungs of cystic fibrosis children.

There have been enormous improvements in life expectancy of patients with cystic fibrosis, especially with improved nutrition and better understanding of the basic cellular defects. However, infection in particular with Pseudomonas aeruginosa and Burkholderia cepacia, has the greatest effect in decreasing life expectancy. Although infections can be prevented by rigorous infection control procedures, early aggressive antimicrobial chemotherapy and established infection managed by antibiotics, they are not completely effective. A greater understanding of how the bacteria evade the host defences and produce infection is needed.

Bacterial Infections↗
PubMed2002

New pathogens.

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Circoviridae↗