Appropriate responses to bioterrorist threats.
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Biomedical subjects
Publications and source records attributed to A Nicoll.
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The HIV-1 infections detected in an ongoing national unlinked anonymous HIV surveillance program were subtyped and analyzed according to demographic and risk characteristics. Of the 893 anti--HIV-1--positive specimens allocated to an exposure group, 70% could be subtyped. Almost 25% of infections subtyped were non-B, mostly subtypes A, C, and D. Non-B infections were rare in homosexual and bisexual men and in drug injectors. Forty percent of infections in heterosexual men attending genitourinary medicine clinics were non-B subtypes; of these, 25% were subtype A infections and 59% were subtype C infections. For female clinic attendees, 61% were non-B subtype infections, of which 48% were subtype A infections and 42% were subtype C infections. Of the clinic attendees born in the United Kingdom and Europe, 14% of the men and 35% of the women were infected with non-B subtypes. In contrast, 78% of infections in antenatal patients were non-B subtypes, of which 61% were subtype A and 29% were subtype C. Extrapolation to the estimated 29,700 prevalent adult infections in the United Kingdom indicates that approximately 8,100 (27%) such infections are non-B subtypes and that these are found almost entirely in heterosexuals. The findings suggest spread of infection of non-B subtypes to heterosexuals born in the United Kingdom from individuals infected in regions of high prevalence.
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BACKGROUND: The optimal control of communicable diseases requires accurate information on incubation periods, periods of infectiousness and the effectiveness of exclusion. We collected the available evidence for a wide range of infections and infestations and produced evidence-based guidelines for their control in schools and preschools. METHODS: A thorough MEDLINE literature search was conducted on the incubation period, period of infectiousness and effectiveness of exclusion for 41 infections. The quality of the information obtained was indicated by levels of evidence. The information was used to produce guidelines on exclusion, and the recommendations were graded according to the levels of evidence available. Grades A, B and C represented strongly, reasonably and poorly evidence-based recommendations, respectively. RESULTS: The quality of data obtained was highly variable. Information on incubation periods was obtained for all 41 infections and was generally of good quality. Information on periods of infectiousness and effectiveness of exclusion was of a lesser quality and was found for only 11 and 4 conditions, respectively. There were 3 Grade A, 17 Grade B and 21 Grade C recommendations on exclusion. Examples of exclusion periods include: 5 days for chickenpox, measles, mumps, rubella, pertussis and scarlet fever; and 24 h from the cessation of diarrhea for most gastrointestinal diseases In contrast to existing guidelines exclusion was not recommended for school age children with hepatitis A. CONCLUSIONS: We have been able to present the best available data on the incubation periods and periods of infectiousness of 41 childhood infections. It was possible to produce strongly or reasonably evidence-based guidelines on exclusion periods for approximately one-half of the infections.
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Primary cultures of intrahepatic bile duct epithelial (IBDE) cells isolated from duckling livers were successfully grown for studies of duck hepatitis B virus (DHBV). The primary IBDE cells were characterized by immunohistochemistry using CAM 5.2, a cytokeratin marker which was shown to react specifically to IBDE cells in duck liver tissue sections and in primary cultures of total duck liver cells. Immunofluorescence assay using anti-duck albumin, a marker for hepatocytes, revealed that these IBDE cultures did not appear to contain hepatocytes. A striking feature of these cultures was the duct-like structures present within each cell colony of multilayered IBDE cells. Normal duck serum in the growth medium was found to be essential for the development of these cells into duct-like structures. When the primary cultures of duck IBDE cells were acutely infected with DHBV, dual-labeled confocal microscopy using a combination of anti-DHBV core proteins and CAM 5.2 or a combination of anti-pre-S1 proteins and CAM 5.2 revealed that the IBDE cell colonies contained DHBV proteins. Immunoblot analysis of these cells showed that the DHBV pre-S1 and core proteins were similar to their counterparts in infected primary duck hepatocyte cultures. Southern blot analysis of infected IBDE preparations using a digoxigenin-labeled positive-sense DHBV riboprobe revealed the presence of hepadnavirus covalently closed circular (CCC) DNA, minus-sense single-stranded (SS) DNA, double-stranded linear DNA, and relaxed circular DNA. The presence of minus-sense SS DNA in the acutely infected IBDE cultures is indicative of DHBV reverse transcriptase activity, while the establishment of a pool of viral CCC DNA reveals the ability of these cells to maintain persistent infection. Taken collectively, the results from this study demonstrated that primary duck IBDE cells supported hepadnavirus replication as shown by the de novo synthesis of DHBV proteins and DNA replicative intermediates.
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OBJECTIVE: To assess the impact of the sexual component of AIDS and HIV campaigns on transmission of HIV and other sexually transmitted infections (STIs). DESIGN: Comparison of time series data. SETTING: England, 1971-1999. OUTCOME MEASURES: HIV transmission and diagnoses among men who have sex with men (MSMs), rates of attendances and specific STI diagnoses (per 100 000 total population) at genitourinary medicine (GUM) clinics. RESULTS: Awareness of AIDS and campaigns in 1983-4 among homosexual men coincided with substantial declines in transmission of HIV and diagnoses of syphilis among MSMs. During general population campaigns in 1986-7 new GUM clinic attendances requiring treatment fell by 117/10(5) in men and 42/10(5) in women. Rates for gonorrhoea fell by 81/10(5) and 43/10(5) and genital herpes by 6/10(5) and 4/10(5), respectively. Previous rises in genital wart rates were interrupted, while rates of attendances not requiring treatment (the "worried well") increased by 47/10(5) and 58/10(5) for men and women, respectively. Since 1987 diagnoses of HIV among MSMs have not declined, averaging 1300-1400 annually. Following a period of unchanging rates there have been substantial increases in GUM attendances requiring treatment, notably for gonorrhoea, syphilis, and viral STIs since 1995. CONCLUSIONS: Self help initiatives and awareness among homosexual men in 1983-4 contributed significantly to a fall in HIV transmission among MSMs, and the general campaigns of 1986-7 were associated with similar effects on all STI transmission. Both effects seem to have occurred through changing sexual behaviour, and probably contributed to the UK's low national HIV prevalence. Bacterial STI incidence has increased significantly since 1995 and there is no evidence that recent prevention initiatives have reduced HIV transmission among MSMs, hence sexual health initiatives need to be comprehensively reinvigorated in England.
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The experience of autumn 2001, when anthrax spores were released in the postal system, had considerable consequences in the United States and in Europe. The threat of covert deliberate releases against civilians has become a reality. In Europe, despite the growing number of criminal hoaxes, no cases of anthrax linked to deliberate releases have been reported, and the only contaminated letters were addressed to American embassies abroad. Nevertheless, the time has come for Europe to set up efficient and timely plans to respond to bioterrorism, under the coordination of the European Commission.
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BACKGROUND: Variant Creutzfeldt-Jakob Disease (vCJD) was first reported in 1996; the youngest patient developed symptoms at 16 years of age. We have done 3 years of prospective active surveillance for progressive intellectual and neurological deterioration (PIND) in UK children, and have searched for vCJD among the children who were reported. METHODS: Since May, 1997, there has been active surveillance for patients younger than 16 years old with PIND by means of a monthly card sent to all UK consultant paediatricians by the British Paediatric Surveillance Unit. Clinical'details of cases of PIND are obtained from reporting paediatricians by telephone interview or site visit, and an expert group of paediatric neurologists then classifies the cases. FINDINGS: After 3 years, 885 patients with suspected PIND have been reported. Among them were two fatal cases of definite vCJD and one case of probable vCJD; all were reported in 1999. One girl was age 12 years at onset--the youngest ever case of vCJD. No other children with the clinical features of vCJD were identified. The expert group has discussed 655 cases, of which 360 have a confirmed underlying cause, being categorised into 88 known neurodegenerative diseases. INTERPRETATION: That this prospective active surveillance in the UK has found few children with suspected vCJD is relatively reassuring. However, 3 years is a short time to survey a disease with an unknown incubation period. Since one probable and two definite cases of vCJD were reported to the study in 1999, there is concern that more childhood cases may appear.
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BACKGROUND: Recent studies have implicated bile duct epithelial cells (BDEC) as a reservoir of hepatitis B virus (HBV) infection that may be particularly important in the development of post-liver transplant recurrence of hepatitis B. The aim of this study was to compare the effects of antiviral therapy on duck HBV (DHBV) expression in hepatocytes and BDEC and to determine if this was affected by biliary hyperplasia. METHODS: Ducklings congenitally infected with DHBV received penciclovir (10 mg/kg per day) treatment from 9 days of age. In order to mimic the biliary hyperplasia that often accompanies severe post-liver transplant HBV recurrence, half the animals underwent bile duct ligation. Duck HBV-DNA in serum was measured at day 1, and serum and liver DHBV-DNA were determined when the animals were killed on day 17. Intrahepatic expression of viral preS1 antigen and DHBV-DNA was measured by immunohistochemistry and in situ hybridization, respectively. RESULTS: Viraemia became undetectable in the penciclovir-treated animals at day 17, following 8 days of therapy. Examination of liver tissue revealed that all hepatocytes and the majority of BDEC contained DHBV preS1 antigen and DHBV-DNA. Penciclovir greatly reduced the intrahepatic viral burden, but there was no antiviral effect on viral markers within BDEC. Despite the increased number of BDEC after bile duct ligation, the same proportion of BDEC was seen to be infected, and this was unaffected by antiviral therapy. CONCLUSIONS: In the duck model with and without biliary hyperplasia, penciclovir controls DHBV replication and reduces viral burden in hepatocytes, but not in BDEC. The BDEC appear to be an important reservoir of virus that is relatively unaffected by antiviral treatment, and may play an important role in disease persistence and relapse following cessation of therapy.
BACKGROUND: In order to monitor the epidemiology of human immunodeficiency virus (HIV), integrated national programmes of unlinked anonymous (blinded) HIV sero-surveys have taken place in the UK since 1990. METHODS: The programmes comprise multi-centre surveys primarily using specimens gathered routinely for screening groups of patients. All specimens are irreversibly unlinked from patient identifiers before being tested. RESULTS: The surveys have met their prime aim of providing at low cost minimally biased estimates of current HIV prevalence and trends in sentinel populations. The surveys have remained acceptable to professionals and the public, being successfully implemented without breech of their founding principles. The findings have had major public health applications, have influenced HIV policy and funding, been used for monitoring the spread of HIV, for targeting and evaluating health promotion and improving projections of severe HIV disease. The surveys have detected substantial prevalence rises and under-diagnosis of HIV which would otherwise have been unrecognised. The programmes' value is being increased by sub-typing HIV-1 isolates, capturing additional demographic information to detect spread among minority groups. The same specimens are used for monitoring other infections (initially hepatitis A, B and C). CONCLUSIONS: Monitoring HIV and other infections through unlinked anonymous HIV surveillance has become an integral essential part of national HIV and AIDS surveillance. Although it has unique applications the value of unlinked anonymous surveillance is maximized when used in conjunction with behavioural data, information from HIV and AIDS reporting, and behavioural data and surveillance for other sexually transmitted infections.
OBJECTIVE: Antenatal screening for syphilis is well established in the United Kingdom. The prevalence of syphilis is now very low, prompting the question as to whether this screening programme is still necessary. This paper aims at identifying possible screening strategy options for the programme and comparing their effectiveness and cost effectiveness. METHODS: The cost of the screening programme in the United Kingdom was estimated. This was based on the cost of screening tests, treatment, and follow up of infected women and their infants. This information was obtained from laboratories, antenatal clinics, and genitourinary medicine clinics. Epidemiological data from a survey of women treated for syphilis in pregnancy were analysed to identify groups at increased risk of syphilis. Strategic options for the screening programme were then identified. The effectiveness, number needed to treat, and cost effectiveness of these options were compared. RESULTS: Antenatal screening in the United Kingdom detected at least 40 pregnant women who need treatment for syphilis every year. This means that 18602 women are screened for every woman detected who needs treatment for syphilis. The marginal annual cost of this screening programme in the United Kingdom is 672366 pounds sterling. This is equivalent to 90p per woman screened, or 16670 pounds sterling to detect one woman who needs treatment for syphilis. The screening programme could be targeted geographically at pregnant women in the Thames regions. This option has the potential to save 482185 pounds sterling. Other strategic options are to target pregnant women in non-white ethnic groups, or those born outside the United Kingdom. These targeted options would each detect between 70% and 77% of women needing treatment for syphilis. These options could potentially save 592938 pounds sterling and 562691 pounds sterling respectively. CONCLUSIONS: Targeting or stopping the screening programme would save relatively little money. Although selectively screening groups by country of birth or by ethnic group could detect at least 70% of cases, this would be politically and practically difficult. Targeting by region would facts and the changing international epidemiology of syphilis lead us to recommend that the current universal antenatal screening for syphilis should continue.
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