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.

Routine versus clinically driven laboratory monitoring of HIV antiretroviral therapy in Africa (DART): a randomised non-inferiority trial.

BACKGROUND: HIV antiretroviral therapy (ART) is often managed without routine laboratory monitoring in Africa; however, the effect of this approach is unknown. This trial investigated whether routine toxicity and efficacy monitoring of HIV-infected patients receiving ART had an important long-term effect on clinical outcomes in Africa. METHODS: In this open, non-inferiority trial in three centres in Uganda and one in Zimbabwe, 3321 symptomatic, ART-naive, HIV-infected adults with CD4 counts less than 200 cells per microL starting ART were randomly assigned to laboratory and clinical monitoring (LCM; n=1659) or clinically driven monitoring (CDM; n=1662) by a computer-generated list. Haematology, biochemistry, and CD4-cell counts were done every 12 weeks. In the LCM group, results were available to clinicians; in the CDM group, results (apart from CD4-cell count) could be requested if clinically indicated and grade 4 toxicities were available. Participants switched to second-line ART after new or recurrent WHO stage 4 events in both groups, or CD4 count less than 100 cells per microL (LCM only). Co-primary endpoints were new WHO stage 4 HIV events or death, and serious adverse events. Non-inferiority was defined as the upper 95% confidence limit for the hazard ratio (HR) for new WHO stage 4 events or death being no greater than 1.18. Analyses were by intention to treat. This study is registered, number ISRCTN13968779. FINDINGS: Two participants assigned to CDM and three to LCM were excluded from analyses. 5-year survival was 87% (95% CI 85-88) in the CDM group and 90% (88-91) in the LCM group, and 122 (7%) and 112 (7%) participants, respectively, were lost to follow-up over median 4.9 years' follow-up. 459 (28%) participants receiving CDM versus 356 (21%) LCM had a new WHO stage 4 event or died (6.94 [95% CI 6.33-7.60] vs 5.24 [4.72-5.81] per 100 person-years; absolute difference 1.70 per 100 person-years [0.87-2.54]; HR 1.31 [1.14-1.51]; p=0.0001). Differences in disease progression occurred from the third year on ART, whereas higher rates of switch to second-line treatment occurred in LCM from the second year. 283 (17%) participants receiving CDM versus 260 (16%) LCM had a new serious adverse event (HR 1.12 [0.94-1.32]; p=0.19), with anaemia the most common (76 vs 61 cases). INTERPRETATION: ART can be delivered safely without routine laboratory monitoring for toxic effects, but differences in disease progression suggest a role for monitoring of CD4-cell count from the second year of ART to guide the switch to second-line treatment. FUNDING: UK Medical Research Council, the UK Department for International Development, the Rockefeller Foundation, GlaxoSmithKline, Gilead Sciences, Boehringer-Ingelheim, and Abbott Laboratories.

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.

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.

Patient notification exercise following a dentist's admission of the periodic use of unsterilized equipment.

During 2001, Greater Glasgow National Health Service (NHS) Board undertook a patient notification exercise in a Glasgow dental practice following the admission, by the dentist, of the use of unsterilized dental equipment on patients. Four thousand and eighty-nine exposed patients were identified; of these, 1696 contacted the NHS helpline and 1005 were counselled and screened for hepatitis C virus (HCV), hepatitis B virus (HBV) and human immunodeficiency virus. One patient showed evidence of previous HBV infection and 13 had antibodies to HCV. Molecular investigation of the HCV isolates indicated no significant associations. The investigation found no evidence of patient-to-patient transmission of HCV among patients attending the practice of a dentist who admitted periodically using unsterilized equipment.

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.

Relationship between HIV-1 Env subtypes A and D and disease progression in a rural Ugandan cohort.

OBJECTIVE: To investigate the role of HIV-1 envelope subtypes on disease progression in a rural cohort of Ugandan adults where two major HIV-1 subtypes (A and D) exist. METHODS: Participants of a clinical cohort seen between December 1995 and December 1998 had blood collected for HIV-1 subtyping. These included prevalent cases (people already infected with HIV at the start of the study in 1990) and incident cases (those who seroconverted between 1990 and December 1998). HIV-1 subtyping was carried out by heteroduplex mobility assay and DNA sequencing in the V3 env region. Disease progression was measured by the rate of CD4 lymphocyte count decline, clinical progression for the incident cases as time from seroconversion to AIDS or death, to first CD4 lymphocyte count < 200 x 10(6)/l and to the World Health Organization clinical stage 3. All analyses were adjusted for age and sex. RESULTS: One hundred and sixty-four individuals, including 47 prevalent and 117 incident cases, had V3 env subtype data of which 65 (40%) were subtyped as A and 99 as D. In the incident cases, 44 (38%) were subtyped as A and 73 as D. There was a suggestion that for most end-points A had a slower progression than D. The cumulative probability of remaining free from AIDS or death at 6 years post-seroconversion was 0.72 [95% confidence interval (CI), 0.50 to 0.85] for A and 0.58 (95% CI, 0.42 to 0.71) for D, and the adjusted hazard ratio of subtype D compared to A was estimated to be 1.39 (95% CI, 0.66 to 2.94; P = 0.39). The estimated difference in rates of decline in square root CD4 lymphocyte counts was -0.41 per year (95% CI, -0.98 to 0.15; P = 0.15). CONCLUSION: This study suggests that although subtype A may have a slower progression than D, HIV-1 envelope subtype is not a major factor in determining the progression of HIV-1 disease in a rural population in Uganda.

An improved algorithm for determining HIV type 1 subtypes in a primary laboratory in Uganda.

A pilot study was undertaken with the objective of developing a simple, economical, and efficient algorithm through which to subtype HIV-1 in a large epidemiological cohort study in Uganda. A peptide enzyme immunoassay (PEIA) employing both V3 and gp41 regions and a heteroduplex mobility assay (HMA) were evaluated in comparison with DNA sequencing. Of 146 samples selected, 115 (79%) were successfully sequenced. Taking sequence data as the "gold standard," other assays were compared with these data. The HMA correctly identified 95 (83%) of the samples, and only 1 sample was wrongly identified. The V3 PEIA alone and in combination with gp41 peptides correctly identified 76 and 78% of the samples, respectively; however, the number of wrongly identified samples was four times less with the combination compared with V3 peptides alone (4 versus 16%). The sensitivity, specificity, and positive and negative predictive values for serotype A and D samples were greater for the combination than V3 peptides alone. We have described a new algorithm to segregate subtypes A and D. This algorithm uses the two peptide assays followed by HMA and then DNA sequencing for untypable samples, giving an accuracy of 95% at a cost of 37 and 21% for consumables compared with subtyping all the samples by HMA or DNA sequencing, respectively. This proposed approach is suitable for epidemiological studies in Uganda and other regions with a predominance of A and D subtypes.

Comparison of the continuous cell line 293 with human embryo kidney cells and human embryo fibroblast cells for the cultivation of ocular viruses.

The continuous cell line 293 was evaluated as a replacement for primary human embryo kidney (HEK) cells in the cultivation of ocular viruses. The 293 cells were found to be as sensitive as HEK cells and human embryo fibroblast (HEF) cells for the cultivation of adenoviruses and herpes simplex virus (HSV) respectively. As a continuous cell line, 293 cells are preferable to HEK and HEF cells for the routine isolation of ophthalmic viruses.

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 response of lambs to experimental infection with Orf virus.

A group of six specific pathogen free (SPF) lambs were infected epidermally with Orf virus. Seven weeks later they were reinfected. For a period of 4 weeks after each inoculation they were observed clinically and blood was collected for analysis of virus specific antibody measured by ELISA and peripheral blood lymphocyte (PBL) proliferative response to various viral antigens. After the primary infection all animals showed clinical signs of Orf, namely vesicle formation which became pustular followed by scabbing; this steadily became heavier prior to shedding and the resolution of the infection by about 4 weeks. The severity of infection varied within the group. Little lymphoproliferative activity was recorded during the primary infection, although five/six test animals had positive lymphoproliferative responses to an sodium dodecyl sulphate (SDS) solubilised scab purified Orf virus preparation at some point between days 7 and 14 after inoculation. All animals seroconverted to Orf virus, lymphoproliferative activity always preceding specific antibody detection. Resolution of the secondary infection was very rapid. Vesicles were visible by day 2 after inoculation which became pustular followed by scab formation and resolution in the majority of animals by day 8. All animals showed a significant (greater than four-fold) rise in specific antibody titre following secondary inoculation. The proliferative activity of PBL's was much greater than that recorded for the primary infection although the magnitude of this response varied greatly between individuals.

Response of efferent lymph and popliteal lymph node to epidermal infection of sheep with orf virus.

Functional and phenotypic changes in the cell populations were monitored in the popliteal efferent lymph of sheep following experimental epidermal infection with orf virus. In another group of sheep, cells from the popliteal lymph node draining the site of infection were similarly monitored and compared with the cells from contralateral popliteal and mesenteric lymph nodes. All sheep showed serological evidence of previous exposure to orf virus. Following infection, anti-orf antibody titres rose and efferent lymphocyte and blast cell output increased. Interferon-like activity was detected in efferent lymph early after orf virus but not mock infection. Lymphocytes from the draining popliteal lymph node showed antigen-specific lymphoproliferation on Days 3-7 while cells in the efferent lymph demonstrated proliferative activity on Days 4-6. The requirement for exogenous antigen-presenting cells in the culture of efferent lymphocytes varied between individual sheep. The culture supernatant from proliferating lymph node cells contained interferon-like activity but no anti-orf antibodies, the reverse of that from cultured efferent lymphocytes, perhaps indicating a different reactive T cell population. During the course of the experiment there was an increase in the percentage of efferent lymphocytes expressing MHC Class II antigens and surface immunoglobulins, the latter being recorded as a double peak. The short-term nature of the local T cell response may in part explain the incompleteness of immunity to orf virus in sheep.

Sexual networks in Uganda: mixing patterns between a trading town, its rural hinterland and a nearby fishing village.

The study was based in south-west Uganda where significant differences in HIV prevalence have been found between urban and rural areas. Longitudinal data collected in a diary format was used to determine the extent to which high-risk men and women living in a truck stop/trading town had sexual contact with people from surrounding rural areas and a nearby fishing village. Study participants were 143 men, 75 of whom were resident in the town, 40 in a fishing village and 28 in rural areas, and 81 women, of whom 47 were resident in the town, 25 in the fishing village and 9 in a rural area. During 1687 man weeks the 143 men made 3149 trips and had 5189 sexual contacts. Ninety-two per cent of these sexual contacts occurred in the man's current place of residence and 21% were with a new partner. The 81 women participated for 1280 women weeks during which they recorded 6378 sexual contacts. Women who lived in the fishing village and the rural area had around 90% of their contacts with local men while those who lived in the town fell into 3 categories: women who charged a relatively high price for commercial sex had only 11% of contacts with men living in the town, while those who charged a tenth of the price had 71% of contacts with town men. The small number of women who fell into an intermediate category, in terms of price, had sexual contact with a wide variety of men. These findings show that there is little scope for HIV infection to spread between different residential or occupational groups. This may help to explain how large differences in HIV seropositivity between neighbouring localities can be maintained for long periods, despite considerable social and economic mixing between groups and high levels of sexual partner change within groups.

PIP: In southwest Uganda, there is concern that sexual mixing between rural areas with low HIV prevalence and urban areas with high HIV prevalence will produce uniformly high rates of HIV. To determine the extent of such mixing, a prospective study was conducted in a trading town on the trans-African highway with a steady flow of male truckers, an agricultural hinterland to the west, and a fishing village to the east. A total of 143 men recruited largely from bars and 81 women reported to be sexually promiscuous kept records of their sexual contacts over a 6-month period. During 1687 man-weeks of observation, the men made 3149 road trips and had 5189 sexual contacts; 92% of these contacts occurred in the men's place of residence and 21% involved a new partner. 59% of town men's sexual contacts, 61% reported by men in the fishing village, and 52% of those in rural areas involved casual partners. An additional 6378 sexual encounters were recorded during 1280 woman-weeks. Close to 90% of women's sexual contacts in the 2 rural areas involved local men. Among the highest-paid town commercial sex workers, only 11% of sexual contacts involved men from the town; in contrast, 71% of sexual encounters among town women who charged only 10% the price of their more expensive counterparts were with local men. Serologic testing of a subset of 75 men and 52 women yielded HIV prevalences of 28% and 52%, respectively. The distinct sexual networks identified in this study suggest it is unlikely that rates of HIV infection in the rural areas will reach those in nearby trading towns.

The stability between two HIV-1 RNA measurements one year apart and the relationship with HIV subtype in rural Uganda.

We compared HIV-1 RNA levels using the nucleic acid sequenced based amplification (NASBA) test kit in 2 samples taken one year apart from participants infected with env subtype A or D in a population-based cohort in Uganda. Fifty participants were infected with subtype A and 70 with subtype D. HIV-1 RNA levels were significantly higher in subtype D unadjusted (P=0.001), and after adjusting for age, gender, and CD4 count (P<0.001). Eighty-six participants had HIV-1 RNA measurements in both years and 67 (78%) were within one log10 of their result a year before. There was no relationship between the difference in log viral load and proportion of CD4 change. Individuals infected with subtype D had a higher average increase in viral load and this was statistically significant if adjusted for baseline levels and CD4 count (P=0.015).

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.

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.