Incidence of hepatitis C virus and HIV among new injecting drug users in London: prospective cohort study.
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Adult↗
Biomedical subjects
Andrew J Hall
Publications and source records attributed to Andrew J Hall.
Rate of first recorded diagnosis of autism and other pervasive developmental disorders in United Kingdom general practice, 1988 to 2001.
BACKGROUND: There has been concern that the incidence of autism and other pervasive developmental disorders (PDDs) is increasing. Previous studies have been smaller, restricted to autism (excluding other pervasive developmental disorders such as Asperger's syndrome), included boys only, or have not been based on a national sample. We investigated time trends in the rates of diagnosis of pervasive developmental disorders. METHODS: We analysed the rates of first diagnosis of pervasive developmental disorders among people registered with a practice contributing to the United Kingdom General Practice Research Database during the period 1988 to 2001. We included 1410 cases from over 14 million person-years of observation. The main outcome measures were rates of diagnosis of pervasive developmental disorders by year of diagnosis, year of birth, gender and geographical region. RESULTS: The rate increased progressively from 0.40/10,000 person-years (95% CI 0.30 to 0.54) in 1991 to 2.98/10,000 (95% CI 2.56 to 3.47) in 2001. A similar change occurred in the age standardised incidence ratios, from 35 (95% CI: 26-47) in 1991 to 365 (95% CI: 314-425) in 2001. The temporal increase was not limited to children born during specific years nor to children diagnosed in a specific time period. The rate of diagnosis of PDDs other than autism rose from zero for the period 1988-1992 to 1.06/10,000 person-years in 2001. The rate of diagnosis of autism also increased but to a lesser extent. There was marked geographical variation in rates, with standardised incidence ratios varying from 66 for Wales to 141 for the South East of England. CONCLUSIONS: Better ascertainment of diagnosis is likely to have contributed to the observed temporal increase in rates of diagnosis of PDD, but we cannot exclude a real increase.
Asperger Syndrome↗
An enantioselective imprinted receptor for Z-glutamate exhibiting a binding induced color change.
Using 1-(4-styryl)-3-(3-nitrophenyl)urea as host monomer for the imprinting of Z-(D or L)-Glu, a polymeric receptor exhibiting strong enantioselectivity and a change in color intensity upon binding of the guest was obtained.
Amino Acids↗
A cohort study of the effectiveness of influenza vaccine in older people, performed using the United Kingdom general practice research database.
BACKGROUND: The effectiveness of influenza vaccination against hospitalization and death can only ethically be assessed in observational studies. A concern is that individuals who are vaccinated are healthier than individuals who are not vaccinated, potentially biasing estimates of effectiveness upward. METHODS: We conducted a historical cohort study of individuals >64 years of age, for whom there were data available in the General Practice Research Database for 1989 to 1999 in England and Wales. Rates of admissions for acute respiratory diseases and rates of death due to respiratory disease were compared over 692,819 person-years in vaccine recipients and 1,534,280 person-years in vaccine nonrecipients. RESULTS: The pooled effectiveness of vaccine against hospitalizations for acute respiratory disease was 21% (95% confidence interval [CI], 17%-26%). The rate reduction attributable to vaccination was 4.15 hospitalizations/100,000 person-weeks in the influenza season. Among vaccine recipients, no important reduction in the number of admissions to the hospital was seen outside influenza seasons. The pooled effectiveness of vaccine against deaths due to respiratory disease was 12% (95% CI, 8%-16%). A greater proportionate reduction was seen among people without medical disorders, but absolute rate reduction was higher in individuals with medical disorders, compared with individuals without such disorders (6.14 deaths due to respiratory disease/100,000 person-weeks vs. 3.12 deaths due to respiratory disease/100,000 person-weeks). Clear protection against death due to all causes was not seen. CONCLUSIONS: Influenza vaccination reduces the number of hospitalizations and deaths due to respiratory disease, after correction for confounding in individuals >64 years of age who had a high risk or a low risk for influenza. For elderly people, untargeted influenza vaccination is of confirmed benefit against serious outcomes.
Aged↗
Validation of the diagnosis of autism in general practitioner records.
BACKGROUND: We report on the validity of the computerized diagnoses of autism in a large case-control study investigating the possible association between autism and the measles, mumps and rubella vaccine in the UK using the General Practitioner Research Database (GPRD). We examined anonymized copies of all relevant available clinical reports, including general practitioners' (GP) notes, consultant, speech therapy and educational psychologists reports, on 318 subjects born between 1973 and 1997 with a diagnosis of autism or a related disorder recorded in their electronic general practice record. METHODS: Data were abstracted to a case validation form allowing for the identification of developmental symptoms relevant to the diagnosis of pervasive developmental disorders (PDDs). Information on other background clinical and familial features was also abstracted. A subset of 50 notes was coded independently by 2 raters to derive reliability estimates for key clinical characteristics. RESULTS: For 294 subjects (92.5%) the diagnosis of PDD was confirmed after review of the records. Of these, 180 subjects (61.2%) fulfilled criteria for autistic disorder. The mean age at first recording of a PDD diagnosis in the GPRD database was 6.3 years (SD = 4.6). Consistent with previous estimates, the proportion of subjects experiencing regression in the course of their development was 19%. Inter-rater reliability for the presence of a PDD diagnosis was good (kappa =.73), and agreement on clinical features such as regression, age of parental recognition of first symptoms, language delay and presence of epilepsy was also good (kappas ranging from.56 to 1.0). CONCLUSIONS: This study provides evidence that the positive predictive value of a diagnosis of autism recorded in the GPRD is high.
Age of Onset↗
Case-control study of the effect of mechanical trauma on the risk of herpes zoster.
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Adolescent↗
The Gambia Liver Cancer Study: Infection with hepatitis B and C and the risk of hepatocellular carcinoma in West Africa.
Hepatocellular carcinoma (HCC) is the most common cancer in The Gambia. Hepatitis B virus (HBV) infection is endemic, with 15% to 20% of the population being chronic carriers, whereas hepatitis C virus (HCV) prevalence is low. We recruited 216 incident cases of HCC and 408 controls from three sites. HBV carriage was present in 61% (129/211) of HCC patients and 16% (64/402) of controls, whereas 19% (36/191) of HCC patients were HCV seropositive compared with 3% (11/382) of controls. HCC patients with HCV were notably older and were more likely to be female than those with HBV. Increased HCC risk was strongly associated with chronic HBV (odds ratio, 16.7; 95% CI, 9.7-28.7), HCV (16.7; 6.9-40.1), and dual infection (35.3; 3.9-323). We interpret the additive nature of risk with coinfection as representative of HBV and HCV acting primarily through shared steps in the multistage process of hepatocarcinogenesis. HCV infection was not observed among younger participants, suggesting a possible cohort effect. Reasons for the striking age and gender differences in HCC associated with HBV compared with HCV are unclear, but transmission patterns and age at exposure may be factors. In conclusion, in a standardized evaluation of well-characterized study participants from The Gambia, most cases of HCC are attributable to HBV (57%), but HCV adds a significant fraction (20%), especially among older patients and females. If HCV transmission is not perpetuated in future cohorts, focusing available resources on HB vaccination efforts could greatly ameliorate a major cause of cancer death in sub-Saharan Africa.
Adult↗
What does epidemiology tell us about risk factors for herpes zoster?
Reactivation of latent varicella zoster virus as herpes zoster is thought to result from waning of specific cell-mediated immunity, but little is known about its determinants in individuals with no underlying immunosuppression. We systematically reviewed studies of zoster epidemiology in adults and analysed data from a large morbidity study to identify factors that might be modulated to reduce the risk of zoster. Annual zoster incidence in population-based studies varied from 3.6-14.2/10(3) in the oldest individuals. Risk factors identified in analytical studies that could explain this variation included age, sex, ethnicity, genetic susceptibility, exogenous boosting of immunity from varicella contacts, underlying cell-mediated immune disorders, mechanical trauma, psychological stress, and immunotoxin exposure. Our review highlights the lack of information about risk factors for zoster. We suggest areas of research that could lead to interventions to limit the incidence of zoster. Such research might also help to identify risk factors for age-related immune decline.
Adolescent↗
EPI vaccines-induced antibody prevalence in 8-9 year-olds in The Gambia.
OBJECTIVES: We evaluated antibody prevalence to measles, polio 1 and 3, and tetanus toxoid antibodies in 8-9 year-old children in The Gambia within the framework of the Gambia Hepatitis Intervention Study (GHIS), a large vaccine trial aimed at evaluating vaccine efficacy against hepatitis B virus (HBV) infection, chronic carriage and primary liver cancer in a high risk population. The results of the present survey were compared with a previous survey performed with the same objectives and same methodology but in different children at 3-4 years of age. METHODS: Four clusters of 200 children each were sampled as representative of the whole country. Children would have received BCG, diphtheria-pertussis-tetanus vaccine (DPT), poliovirus vaccine (OPV), measles and yellow fever immunization. The measles haemoagglutination inhibition test (HAI) was used to detect measles antibody. Antibodies to polioviruses 1 and 3 were tested using the standard polio neutralization assay described in the EPI manual (WHO 1990). An enzyme-linked immuno-sorbent assay (ELISA) was used to measure tetanus toxoid antibodies. RESULTS: A high proportion of children were fully vaccinated in both age groups. Measles antibody concentrations were < or =1 : 8 in 8.2% of 8-9 year-old vaccinated children. In the previous survey of 3-4 year-old children this was 11.3%. In the present survey, GMC was lower than in the 3-4 year-old children; 88% of 3-4 year-olds and 89% of 8-9 year-olds had detectable antibody levels against poliovirus type 1. Fewer children at 8-9 years of age had antibodies against poliovirus type 3 than 3-4 year-olds (78%vs. 89% P < 0.001). A significant overall lower proportion of 8-9 year-old children had detectable tetanus toxoid antibodies compared to 3-4 year-old children (87%vs. 95% P < 0.001), as well as those who received four doses of DPT (90%vs. 97% P < 0.001). Conclusions High vaccine coverage is achieved in The Gambia with EPI. With time the number of vaccinated children who are not protected against measles, poliovirus 3 and tetanus increases. Besides the maintenance of high vaccine coverage in infants and young children, booster doses of some of the EPI vaccines in adolescents should be considered.
Antibodies, Bacterial↗
Postweaning exposure to aflatoxin results in impaired child growth: a longitudinal study in Benin, West Africa.
Aflatoxins are dietary contaminants that are hepatocarcinogenic and immunotoxic and cause growth retardation in animals, but there is little evidence concerning the latter two parameters in exposed human populations. Aflatoxin exposure of West African children is known to be high, so we conducted a longitudinal study over an 8-month period in Benin to assess the effects of exposure on growth. Two hundred children 16-37 months of age were recruited from four villages, two with high and two with low aflatoxin exposure (50 children per village). Serum aflatoxin-albumin (AF-alb) adducts, anthropometric parameters, information on food consumption, and various demographic data were measured at recruitment (February) and at two subsequent time points (June and October). Plasma levels of vitamin A and zinc were also measured. AF-alb adducts increased markedly between February and October in three of the four villages, with the largest increases in the villages with higher exposures. Children who were fully weaned at recruitment had higher AF-alb than did those still partially breast-fed (p < 0.0001); the major weaning food was a maize-based porridge. There was no association between AF-alb and micronutrient levels, suggesting that aflatoxin exposure was not accompanied by a general nutritional deficiency. There was, however, a strong negative correlation (p < 0.0001) between AF-alb and height increase over the 8-month follow-up after adjustment for age, sex, height at recruitment, socioeconomic status, village, and weaning status; the highest quartile of AF-alb was associated with a mean 1.7 cm reduction in growth over 8 months compared with the lowest quartile. This study emphasizes the association between aflatoxin and stunting, although the underlying mechanisms remain unclear. Aflatoxin exposure during the weaning period may be critical in terms of adverse health effects in West African children, and intervention measures to reduce exposure merit investigation.
Benin↗
A substructure approach toward polymeric receptors targeting dihydrofolate reductase inhibitors. 2. Molecularly imprinted polymers against Z-l-glutamic acid showing affinity for larger molecules.
The preparation of a molecularly imprinted polymer against N-Z-L-glutamic acid using a novel bis-urea functional monomer is described. The polymer exhibits affinity for the template over N-Z-protected aspartic acid and glycine and, further, is capable of binding larger molecules, e.g., the anti-cancer drug methotrexate, containing the glutamate substructure.
Enzyme Inhibitors↗
Liver cancer in low and middle income countries.
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Aflatoxins↗
Efficacy of polysaccharide pneumococcal vaccine in adults in more developed countries: the state of the evidence.
We review studies on the efficacy against disease caused by Streptococcus pneumoniae of the 23-valent polysaccharide pneumococcal vaccine in adult populations in the more developed countries. Meta-analyses of primary vaccine trials have attempted to reduce uncertainty from lack of power. Vaccine efficacy calculated from studies in South African gold-miners and in Papua New Guinea, with high attack rates and differing serotype patterns, cannot automatically be applied to more developed countries. Meta-analyses will overestimate a protective effect if this clinical heterogeneity is ignored. Meta-analyses limited to trials in the more developed setting show no protective effect against pneumococcal pneumonia and a non-significant protective effect against bacteraemia. Lack of a specific diagnosis limits the ability to detect a protective effect against pneumococcal pneumonia. Most, but not all, observational studies confirm a protective effect against bacteraemia. An effect on mortality in more developed countries has yet to be documented.
Adult↗
Vaccination politics.
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Financing, Organized↗
Incidence and risk factors of paediatric rotavirus diarrhoea in northern Ghana.
We measured the type-specific incidence of paediatric rotavirus diarrhoea in an area of northern Ghana. Over 1 year, diarrhoea 1717 episodes were identified, of which 677 (39%) were positive for rotavirus. Risk factors for rotavirus infection included old age, wasting, high Vesikari score and the episode occurring in the dry season. Rotavirus-positive episodes tended to be more acute, causing vomiting and greater dehydration, and were more likely to require hospitalization. The incidence was 0.089 episodes per person-year for all diarrhoea, and 0.035 for rotavirus diarrhoea. The observed incidence decreased markedly with distance from the nearest health centre, suggesting a large unobserved burden. G2P[6], G3P[4] and G9P[8] made up more than half the genotypes detected, but the remainder were diverse. There is a large burden of rotavirus diarrhoea, but the effectiveness of future vaccines could be diluted by the high polymorphism of the virus, and the difficulty of reaching remote populations.
Child, Preschool↗
Mortality of hepatitis B surface antigen-positive blood donors in England and Wales.
BACKGROUND: Large population-based cohort studies in areas of high hepatitis B virus (HBV) prevalence have provided the evidence establishing hepatitis B surface antigen (HBsAg) carriage as a risk factor for hepatocellular carcinoma (HCC) and liver disease. Fewer studies have examined this in Western countries, where both HBV infection and carriage are less common and transmission patterns differ. This is the only prospective population-based study to examine this relationship in Europe. METHODS: In all, 2681 male and 977 female blood donors in England and Wales, found to be HBsAg positive during routine blood-donation screening, were followed up from recruitment in 1970-1982 to December 1999 and their cause-specific mortality was analysed. This was compared with that of the general population of England and Wales. RESULTS: During a mean of 22 years of follow-up, 17.4% of the 420 deaths were due to HCC or liver disease. There were 20 deaths from HCC in male HBsAg carriers, representing a significantly high standardized mortality ratio (SMR) compared to the male population of England and Wales of 26 (SMR = 26.26; 95% CI: 16.04- 40.54). The HCC incidence rate in males was 33.5 per 100 000 person years and 4.4 per 100 000 person years in females. Men had 8.5 (SMR = 8.50; 95% CI: 6.25- 11.31) and women had 3.9 times the risk of death from liver disease (SMR = 3.89; 95% CI: 1.26-9.09). The risk of circulatory disease deaths was reduced in both males and females. There was a significant increased risk of non-Hodgkins lymphoma that was not apparent in the first decade of follow-up. The increased risk of HCC and liver disease in men fell with follow-up. CONCLUSION: Hepatitis B surface antigen carriage is a significant risk factor in England and Wales for both liver disease and HCC mortality. However, this risk has declined with duration of follow-up. This could be due to natural reversion to HBsAg negativity or as a result of treatment and avoidance of other risk factors. The increased risk of non-Hodgkins lymphoma seen in longer follow-up is likely to be related to HIV infection acquired subsequent to recruitment.
Adolescent↗
Diagnosis of pneumococcal pneumonia by psaA PCR analysis of lung aspirates from adult patients in Kenya.
psaA is the gene encoding pneumococcal surface adhesin A (PsaA), a 37-kDa protein expressed on the surface of Streptococcus pneumoniae. PCR primers for psaA have been shown to amplify the target DNA sequence in all 90 serotypes of S. pneumoniae and in none of 67 heterologous pathogens and colonizing bacteria of the upper respiratory tract. Pathogenic bacteria identified in lung aspirate specimens cannot normally be dismissed as contaminants or colonizers, which limit the assay specificity of other respiratory tract specimens. psaA PCR analysis was evaluated in 171 lung aspirates from Kenyan adults with acute pneumonia. The limit of detection was one genome equivalent. Sensitivity, estimated in 35 culture-positive lung aspirates, was 0.83 (95% confidence interval, 0.70 to 0.95). psaA PCR analysis extended the number of identifications of S. pneumoniae in lung aspirates from 35 on culture to 61 by both methods. Of 26 new pneumococcal diagnoses, 19 were corroborated by results of blood culture or urine antigen detection. Sequences of the PCR products from 12 positive samples were identical to the psaA target gene fragment. Using an internal control for the PCR, inhibition of psaA PCR was demonstrated in 17% (8 of 47) of false-negative specimens. The results of a control PCR for the human gene beta-actin suggested that false-negative psaA PCR results are attributable to problems of specimen collection, processing, or DNA extraction in 30% of cases (14 of 47). psaA PCR analysis is a sensitive tool for diagnosis of pneumococcal pneumonia in adults.
Adhesins, Bacterial↗
Modification of immune function through exposure to dietary aflatoxin in Gambian children.
Aflatoxins are immunotoxins that frequently contaminate staple foods in The Gambia and other parts of sub-Saharan Africa, resulting in high exposure throughout life. Impaired infant immune system development may be a key predictor of mortality from infectious disease. In this study we aimed to determine the effect of dietary aflatoxin exposure on a number of immune parameters in Gambian children. A cohort of 472 Gambian children 6-9 years of age was recruited. Serum aflatoxin-albumin (AF-alb) adducts were analyzed to provide a measure of exposure. Immune parameters included secretory IgA (sIgA) in saliva, cell-mediated immunity (CMI), determined using the CMI multitest where test antigens are applied to the skin, and antibody responses to both rabies and pneumococcal polysaccharide vaccines. Birth weight, current anthropometry, and micronutrient status were also recorded. AF-alb adducts were detected in 93% of the children (geometric mean level 22.3 pg/mg; range 5-456 pg/mg). AF-alb level was strongly influenced by month of sampling. In a multivariable analysis, sIgA was markedly lower in children with detectable AF-alb compared with those with nondetectable levels [50.4 micro g/mg protein (95% confidence interval [CI] 48.0-52.8) and 70.2 micro g/mg protein (95% CI 61.1-79.2), respectively; p < 0.0001]. Antibody response to one of four pneumococcal serotypes, but not rabies vaccine, was weakly associated with higher levels of AF-alb. There was no association between CMI responses to test antigens and AF-alb. These data confirm that children in rural Gambia are frequently exposed to high levels of aflatoxin. The study provides evidence that sIgA in saliva may be reduced because of dietary levels of aflatoxin exposure. Given the high burden of infection-related mortality in West Africa, further investigation of the immune effects of aflatoxin exposure in children is merited.
Aflatoxins↗