Prison and community outbreak of severe respiratory infection due to adenovirus type 14p1 in Tayside, UK.

BACKGROUND: This report describes the investigation and public health management of a community-based outbreak of severe adenovirus serotype 14p1 respiratory infection affecting the Tayside area during 2011. It is the first report of an adenovirus outbreak involving prisons. METHODS: An outbreak-based/incident management approach was carried out. Alerts were sent out to local doctors, general practitioners, prison healthcare staff and consultants so that cases could be identified prospectively. Sequencing of hexon, fibre and E1A regions of adenovirus were carried out to genotype the viruses. RESULTS: Fifteen cases were identified in total, including 13 confirmed cases and 2 possible cases. There were 3 deaths amongst the 13 confirmed cases, with a case fatality rate of 23%. Eight of the cases had a direct association with one of the two prisons in the area. CONCLUSIONS: We advise that surveillance measures for adenovirus infection and guidelines for the management of critically ill patients should be developed in order to identify outbreaks at an early stage and allow patients to receive appropriate treatment. Adenovirus infection should be borne in mind as a cause of severe pneumonia in closed settings such as prisons.

Increased reports of Mycoplasma pneumoniae from laboratories in Scotland in 2010 and 2011 - impact of the epidemic in infants.

In common with reports from other European countries, we describe a substantial increase in the number of laboratory reports of Mycoplasma pneumoniae in Scotland in 2010 and 2011. The highest number of reports came from those aged one year and younger. However, reports from young children were more likely to come from PCR testing than serological testing.

Human immunodeficiency virus 1 subtypes detected in Scottish blood donors.

The aim of our study was to determine human immunodeficiency virus 1 subtypes in Scottish blood donors. We were able to document virus subtypes present in this population over a period of 19 years and examine associated risk factors where available. Subtype B was found to be the predominant cause of human immunodeficiency virus 1 infection in Scottish blood donors with subtype C increasing in this population after 2002. Non-B subtypes were found mainly in heterosexuals but also in all other risk categories with the exception of men having sex with men (MSM). Within Scotland there is an increase in transmission via heterosexual contact and the consequential introduction of non-B subtypes.

HIV subtypes in Scotland, 2000-2006.

The purpose of this study was to document the dynamics of HIV-1 subtypes in Scotland over a 6-year period. Viral RNA from all-new diagnoses was amplified by nested PCR and sequenced in the gag and/or env regions. Subtype was assigned by phylogenetic analysis, and aligned with demographic data including likely route and geographical origin of infection. We present data on 80% of all new diagnoses in Scotland between April 2000 and April 2006. Within the background of an expanding epidemic, subtype B predominates in men who have sex with men and intravenous drug users but there is a small but consistent number of UK-acquired infections in these risk groups caused by non-B subtypes. In heterosexuals, non-B subtypes acquired abroad, especially Africa, are still the largest group but again UK-acquired numbers are rising. The social and clinical significance of the spread of non-B subtypes in different ethnic and risk groups remains to be established.

Association between active GB virus-C (hepatitis G) infection and HIV-1 disease in Uganda.

Although not linked to a disease, GB virus-C viraemia has been associated with an improved prognosis in HIV-1-co-infected individuals. Most studies have been conducted on men (men who have sex with men or injection drug users) infected with HIV-1 subtype B, whereas here we report on both male and female subjects from rural Uganda, predominantly infected via the heterosexual route with HIV-1 subtypes A and D. In a longitudinal study of 272 participants, 47 were GBV-C positive and 181 negative, as determined by reverse transcription-polymerase chain reaction, in both of two plasma samples taken a median of 5.0 years apart. The remainder either acquired (25) or cleared (19) infection. Multilevel regression analyses and Cox survival analyses revealed that participants chronically infected with GBV-C had a slower decline in CD4(+) T cells (P<0.001) and increased survival time (P=0.041) compared with GBV-C RNA-negative, HIV-positive adults. We show that the association between active GBV-C co-infection and improved survival of HIV-1-infected adults is not restricted to HIV subtype B, but is also observed in both males and females infected with HIV subtypes A and D.

HIV-1 subtype in Scotland: the establishment of a national surveillance system.

Historically, subtype B viruses in men who have sex with men (MSM) and injecting drug users (IDU) dominated the HIV epidemic in the United Kingdom, whereas non-B heterosexual infections dominate globally. Heterosexual contact is now the most common route of transmission in the United Kingdom. Here we monitor HIV subtype in Scotland, and link it to origin of infection. HIV-1 sequence was generated from new diagnoses and the subtype thus obtained linked with demographic data. Virus was subtyped from 80% (137/171) of all new diagnoses in Scotland. Of 58 individuals infected by heterosexual contact, 74% (43) harboured non-B viruses, contrasting with 7% (5/68) of those infected by IDU or MSM. Eighty-four per cent of non-Bs (46/55) were probably acquired outside the United Kingdom, but nine individuals probably acquired their non-B infection in the United Kingdom. Non-B subtypes of HIV-1 predominate in recently diagnosed, heterosexually acquired infections in Scotland and are present in all risk groups, even those with no exposure outside the United Kingdom.

Method used to identify previously undiagnosed infections in the HIV outbreak at Glenochil prison.

Four years after the occurrence of an outbreak of hepatitis B and HIV infection among injecting drug user inmates at Her Majesty's Prison Glenochil in Scotland, a study design was developed to complete the epidemiological account of the HIV outbreak. Our aim was to identify potential cases of (1) HIV transmission not diagnosed during the original outbreak investigation and (2) the source(s) of the outbreak. Scotland's HIV positive case register was searched for matches to a soundexed list of 636 Glenochil inmates imprisoned during January-June 1993. Eight HIV infections that may have been acquired in Glenochil and four possible sources of the outbreak were identified. The second stage of follow-up molecular epidemiological techniques used on stored sera samples from identified individuals is described in the companion paper. Without breach of medical or prisoner confidentiality, indirect and anonymous follow-up has proved possible for the Glenochil inmates.

Completing the molecular investigation into the HIV outbreak at Glenochil prison.

In a molecular investigation into the outbreak of HIV in Glenochil during the first 6 months of 1993, we previously demonstrated that 13 out of the 14 HIV positive inmates were infected with a virtually identical strain, and discounted 2 others as potential sources. Here we investigate a further 8 potential contacts and 4 potential sources which were identified in the companion paper. We were able to examine viral sequence from all but one of these 12 and results have revealed them to be distinct both from each other and the original 14. Thus, despite an intensive follow-up investigation, we have been unable to identify any further HIV infections that might have been part of the 1993 outbreak. It is possible that persons who were infected at that time remain undetected; however this and the companion report strongly suggest that if this were the case the likely numbers would be few.

Effect of chemokine receptor mutations on heterosexual human immunodeficiency virus transmission.

To assess the effect of mutations at the CCR-2 and CCR-5 loci on heterosexual human immunodeficiency virus (HIV) transmission, 144 persons heterosexually exposed to HIV (infected and uninfected [EU]) and 57 HIV-positive index partners were genotyped. A significantly higher frequency of 64I heterozygotes at CCR-2 was observed in HIV-positive than in EU women (P=.02, relative risk=1.6). The allele frequency of 64I in women was 8% in HIV-positive contacts and 1% in EUs (P<.02). At CCR-5, no difference in the frequency of Delta32 was seen between groups, and the CCR-5 genotypes did not differ in accumulated "at-risk" exposure in EUs. Combining the analysis of the Delta32 and 64I mutations in index partners suggested an additive effect on transmission (P=.10). Thus heterozygosity for 64I at CCR-2 acts as a risk factor for HIV infection of women after heterosexual contact but heterozygosity for Delta32 at CCR-5 has no detectable effect.

Viral subtype and heterosexual acquisition of HIV infections diagnosed in Scotland.

OBJECTIVE: As at December 1998, 87% of the estimated 33 million people living with HIV throughout the world resided in Africa and South East Asia. In Scotland (and the United Kingdom), a major public health concern has been that non-B subtypes of HIV which predominate in the regions above might enter the country and spread heterosexually among the indigenous population. The authors conducted an investigation to determine if, and to what extent, such transmission had occurred. METHODS: Stored blood samples from people who were diagnosed as HIV positive in central Scotland during 1995-7 and who were reported to have acquired their infection heterosexually, were identified. Sequence data were sought from each sample and, where obtained, viral subtype was assigned. For each case, viral subtype was linked to corresponding epidemiological details on heterosexual risk. RESULTS: Viral sequence was obtained from specimens for 53 of 59 cases. For 43 of the 53 cases, information on region of sexual contact was known. All 19 cases who had a sexual risk in Africa or Asia had a non-B subtype (A, C, or E) while 20 of 24 cases who did not report sexual contact in these regions had a B subtype (p < 0.0001). Of the remaining 10 cases, nine had a subtype B and one a subtype C virus. CONCLUSION: There is no evidence that non-B viral strains from developing countries have yet disseminated appreciably among indigenous heterosexual men and women within Scotland. Continuing to collect both demographic and molecular data from indigenous heterosexuals who are newly diagnosed with HIV would improve the chances of detecting rapidly any appreciable dissemination of non-B subtypes among this population if it were to occur. Such information would be helpful in informing HIV prevention strategies.

Molecular epidemiological analysis of HIV in sexual networks in Uganda.

OBJECTIVE: To investigate the suitability of HIV sequence analysis, based on the p17 region of the gag gene, to characterize the sexual networks in and around a trading town in south-west Uganda. METHODS: Blood samples were obtained from 54 HIV-seropositive members of three distinct sexual networks and phylogenetic analysis carried out on proviral DNA sequences obtained from the p17 region of gag from 53 individuals. RESULTS: Despite documented evidence of very little sexual mixing between residents of the trading town, fishing village and surrounding rural area, there was no evidence of clustering of sequences associated with place of residence. More strikingly, known sexual partners failed to show significantly related sequences, and the two pairs of sequences that did show significant similarity came from individuals who had no known social or sexual contact. CONCLUSIONS: Sequence analyses such as those described here have proved effective in confirming or identifying epidemiological links not only following single transmission events but also within risk groups. However, the results from Uganda contrast markedly with those from Europe and the United States. The length of time that the community has been infected, the number of occasions when the virus has been introduced and the high degree of partner change may contribute to the lack of supportive evidence for sociological studies of sexual networks in Uganda.

Molecular investigation into outbreak of HIV in a Scottish prison.

OBJECTIVES: To support already established epidemiological links between inmates of Glenochil prison positive for HIV infection by using molecular techniques and thus provide evidence of the extent of acquisition during a recent outbreak of the disease resulting from needle sharing. To identify possible sources of the outbreak, and to demonstrate the ability of the methodology to make further links beyond the original outbreak. DESIGN: Viral sequences obtained from the blood of HIV positive prisoners previously identified by standard epidemiological methods were compared with each other and with sequences from other Scottish patients. SETTING: Glenochil prison for men, central Scotland. SUBJECTS: Adult inmates and their possible contacts. RESULTS: Phylogenetic analysis of viral sequences in two different genomic regions showed that 13 of the 14 HIV positive prisoners had been infected from a common source. Previous research had shown that six of these had acquired their infection in Glenochil; molecular evidence suggests that more than double this number were infected while incarcerated. Virus from two long term HIV positive patients who were in the prison at the time of the outbreak but who were not identified in the original or subsequent surveys was sufficiently different to make it unlikely that they were the source. A viral sequence from heterosexual transmission from one inmate showed the ability of these techniques to follow the infection through different routes of infection. CONCLUSION: The number of prisoners infected with HIV during the 1993 outbreak within Glenochil prison was more than twice that previously shown. This shows the potential for the spread of bloodborne diseases within prisons by injecting drugs.

A novel strategy for determining protective antigens of the parapoxvirus, orf virus.

We investigated the feasibility of using vaccinia virus (VAC) recombinants containing large multigene fragments of orf virus DNA to identify protective antigens of orf virus (OV). Sixteen OV strain NZ2 DNA fragments with an average size of 11.4 kb were recombined into VAC strain Lister. Each fragment was mapped relative to OV restriction endonuclease maps but was otherwise uncharacterized. Together the recombinants represent 95% of the OV genome in an overlapping manner. Immunofluorescence showed all 16 constructs expressed products recognized by OV antiserum and radioimmune precipitation with the same antiserum allowed the localization of the major antigens of OV to specific recombinants. These data indicated the approximate genomic locations of the genes encoding the OV major antigens and showed that their expression was authentic rather than resulting from read through from VAC sequences adjacent to the site of recombination. Vaccination of OV-naive sheep with the recombinant library provided protection against a subsequent challenge with virulent OV. These data confirm the feasibility of the proposed strategy.

Natural transmission of orf virus from clinically normal ewes to orf-naive sheep.

The apparent natural transmission of orf virus from clinically normal ewes to susceptible sheep was observed during a border disease vaccine experiment. The 14 susceptible sheep were persistently infected with border disease virus and had been reared indoors in isolation from other sheep since birth. Their ages ranged from two to four years and they were housed in two groups; group 1 consisted of four sheep persistently infected with the Moredun strain of border disease virus and group 2 consisted of 10 sheep persistently infected with the Oban strain of the virus. On day 0, six sheep were removed from group 2 and rehoused. To the remaining four sheep in each group were added eight four- to six-year-old pregnant conventionally reared ewes at 48 days gestation. Fourteen days later the four sheep in group 1 were moved to another pen housing eight similar five-year-old pregnant ewes at 48 days' gestation, and the four sheep from group 2 were rehoused with their original stallmates. Twenty-one days later lip lesions typical of orf were first observed on the sheep from both groups and the disease spread to all the sheep persistently infected with border disease virus over the next four weeks. Virological and serological evidence demonstrated that the source of infection for the sheep was almost certainly the conventionally reared ewes, on which no lesions resembling orf were observed at any time during the study.

The restricted IgG1 antibody response to maedi visna virus is seen following infection but not following immunization with recombinant gag protein.

Maedi-visna (MVV) is a retrovirus of the subfamily lentivirinae which includes HIV, simian immunodeficiency virus (SIV) and feline immunodeficiency virus (FIV). Infection of its natural host, the sheep, does not cause overt immunodeficiency, but rather a chronic inflammatory disease. However, subtle immunological changes following infection have been reported including a sheep IgG1 subclass-restricted MVV-neutralizing antibody. Here we demonstrate by Western blotting that there is no IgG2 serum antibody response to any MVV antigen after MVV infection, in contrast to infection with the parapox virus Orf, when serum IgG2 anti-Orf antibody is readily detected. By ELISA, the IgG1 antibody titres to Orf are higher than to MVV, but the minimum MVV serum antibody IgG1/IgG2 ratio is significantly raised compared with that for Orf virus antibody in the same sheep, indicating that the IgG2 defect in MVV infection cannot be accounted for by differences in the sensitivity of the Orf and MVV ELISA. Serum IgG2 anti-MVV gag p. 25 can be detected in both normal and MVV-infected sheep following immunization with purified recombinant MVV gag p 25 protein in Freund's complete adjuvant. The failure to make an IgG2 MVV-specific antibody indicates that immunological dysfunction can arise with macrophage tropic lentiviruses, and it may aid viral persistence.

Lack of cross-protection between vaccinia virus and orf virus in hysterectomy-procured, barrier-maintained lambs.

Hysterectomy-procured, barrier maintained lambs were immunised with either of virus or vaccinia virus and subsequently challenged with both viruses. Under these conditions lambs were protected from challenge with the homologous virus but no cross-protection was observed. The feeding of colostrum that contained antibodies to orf virus had no effect on the duration of viral lesions. Immunoblotting analysis and ELISA of serum samples taken during the course of the experiment indicated that the animals mounted antibody responses to both viruses. The cross recognition of 3 vaccinia virus antigens by the hyperimmune anti-orf virus serum was revealed by immunoblotting.

Immune responses of patients to orf virus infection.

Orf is a disease of sheep and goats which is caused by a parapox virus. It can be transmitted to humans, and is considered an occupational hazard by those handling sheep. In this paper we present the first report of both cell-mediated and humoral immune responses to naturally acquired orf virus infection in humans. Lymphoproliferative responses of peripheral blood mononuclear cells of patients to an orf virus antigen were vigorous soon after infection, but rapidly declined. Orf virus antibody levels, detected by ELISA, were shown to rise during infection. Western blot analysis confirmed this, and demonstrated that the antibody produced in response to the infection was directed against the 40-kDa viral surface tubule protein. Where direct comparisons were possible, the immune response of humans to orf virus infection was similar to that previously reported for sheep. Evidence was obtained suggesting that prior exposure to vaccinia virus (smallpox vaccination) provided no protection from subsequent orf virus infection. In addition, orf virus infection did not enhance immune responses to vaccinia virus antigens.

Experimental in vivo generation of intertypic recombinant strains of HSV in the mouse.

The primary replication of one strain of HSV was generally unaffected by the simultaneous inoculation of another strain either at the same site or at a different site within the same dermatome. Exceptions to this were the result of the generation of intertypic recombinants which were readily isolated only from sensory ganglia 5 and 6 days after inoculation with a mixture of HSV-1 and HSV-2 and from explant culture of the resultant latently infected ganglia. By restriction enzyme analysis the majority of the recombinant strains from primary infection were characterized as HSV 1; all those from latently infected ganglia were characterized as type 2.