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Genetic polymorphisms of the LMP/TAP gene coded by the HLA-II region may be associated with outcomes of HBV infection. We conducted a case-control study to test the hypothesis, including a persistent group of 155 patients with chronic hepatitis B and 36 healthy carriers, a recovered group of 165 individuals spontaneously recovered from HBV infection, and an uninfected group of 278 healthy normal controls. Genotypes of eight polymorphisms of the LMP/TAP gene were analysed by PCR–RFLP. A logistic regression model was used to analyse statistical differences in polymorphisms or haplotypes in different groups. Of the eight polymorphisms, two (TAP1 codon 637 and LMP7 codon 145) were observed to have statistically significant association with outcomes of HBV infection (P<0·05). The two-locus haplotype constructed with two such polymorphisms was analysed. The frequencies of haplotypes B (Asp-Lys), C (Gly-Gln), and D (Gly-Lys) were found to be increased significantly in the persistent group, compared to healthy controls (OR 2·26, 95% CI 1·62–3·15, P<0·001; OR 2·37, 95% CI 1·69–3·32, P<0·001; OR 4·38, 95% CI 1·78–10·77, P=0·001, respectively). The prevalence of haplotypes B (Asp-Lys), C (Gly-Gln), and D (Gly-Lys) were also significantly higher in the persistent infectious group than in the recovered group (OR 2·68, 95% CI 1·81–3·98, P<0·001; OR 2·40, 95% CI 1·62–3·55, P<0·001; OR 3·03, 95% CI 1·22–7·55, P=0·017, respectively). These findings indicated that genetic polymorphisms of the LMP/TAP gene might be an important factor in determining the outcome of HBV infection.
A universal hepatitis B vaccination programme has been conducted in Long An county since 1986. To investigate the epidemiological changes in hepatitis B virus (HBV) infection we conducted a serosurvey there in 2005. A total of 4686 subjects were enrolled and vaccination history and blood samples collected. HBV infective markers were determined by radioimmunoassay. The results were compared with the data of 1985. Our results show that the overall HBsAg prevalence was 7·5%, less than half of the prevalence reported in 1985. HBsAg and anti-HBc antibody prevalence in people born after 1985 decreased markedly. The gender difference in HBsAg prevalence was abolished in subjects aged <20 years. The administration of a first dose of vaccine within 24 h could reduce the HBsAg prevalence by half. In conclusion, the marked epidemiological changes in HBV prevalence found in this serosurvey indicate that the implementation of HBV vaccination was highly successful.
Inadequate notification is a recognized problem of measles surveillance systems in many countries, and it should be monitored using multiple data sources. We compared data from three different surveillance sources in 2007: (1) the sentinel surveillance system mandated by the Act on Prevention of Infectious Diseases and Medical Care for Patients Suffering Infectious Diseases, (2) the mandatory notification system run by the Aichi prefectural government, and (3) health insurance claims (HICs) submitted to corporate health insurance societies. For each dataset, we examined the number of measles cases by month, within multiple age groups, and in two categories of diagnostic test groups. We found that the sentinel surveillance system underestimated the number of adult measles cases. We also found that HIC data, rather than mandatory notification data, were more likely to come from individuals who had undergone laboratory tests to confirm their measles diagnosis. Thus, HIC data may provide a supplementary and readily available measles surveillance data source.
Optimal antiretroviral strategies for HIV-infected patients still need to be established. To this end a decision tree including different antiretroviral strategies that could be adopted for HIV-infected patients was built. A 10-year follow-up was simulated by using transitional probabilities estimated from a large cohort using a time-homogeneous Markov model. The desired outcome was for patients to maintain a CD4 cell count of >500 cells/mm3 without experiencing AIDS or death. For patients with a baseline HIV viral load ⩾5 log10 copies/ml, boosted protease inhibitor-based immediate highly active antiretroviral therapy (HAART) allowed them to spend 12% more time with CD4 ⩾500/mm3 than did delayed HAART (6·40 vs. 5·69 and 5·57 vs. 4·90 years for baseline CD4 ⩾500 and 350–499/mm3, respectively). In patients with a baseline HIV viral load ⩽3·5 log10 copies/ml, delayed HAART performed better than immediate HAART (6·43 vs. 6·26 and 5·95 vs. 5·18 for baseline CD4 ⩾500 and 350–499/mm3, respectively). Immediate HAART is beneficial in patients with a baseline HIV viral load ⩾5 log10 copies/ml, whereas deferred HAART appears to be the best option for patients with CD4 ⩾350/mm3 and baseline HIV viral load <3·5 log10 copies/ml.
Staphylococcus aureus is a leading cause of infections in deployed service members. Based on a molecular epidemiological study of 182 MRSA isolates from patients in three U.S. Army combat support hospitals in separate regions in Iraq, USA300 clone was the most predominant (80%) pulsotype. This finding suggested that strain carriage from the home country by military personnel is epidemiologically more important than local acquisition.
We developed an individual-based (IB) model to explore the stochastic attributes of state transitions, the heterogeneity of the individual interactions, and the impact of different network structure choices on the poliovirus transmission process in the context of understanding the dynamics of outbreaks. We used a previously published differential equation-based model to develop the IB model and inputs. To explore the impact of different types of networks, we implemented a total of 26 variations of six different network structures in the IB model. We found that the choice of network structure plays a critical role in the model estimates of cases and the dynamics of outbreaks. This study provides insights about the potential use of an IB model to support policy analyses related to managing the risks of polioviruses and shows the importance of assumptions about network structure.
To evaluate the prevalence of hepatitis C virus (HCV) and/or hepatitis B virus (HBV) infections in HIV-infected patients in China, an epidemiological serosurvey was conducted from May 2007 to September 2008 using a random cluster sampling design of infectious disease hospitals in seven high HIV-prevalent provinces (municipalities). Univariate analysis and logistic regression were used to study the determinants of HIV and HBV and/or HCV co-infection. The overall prevalence was 41·83% (95% CI 40·36–43·30) for anti-HCV and 12·49% (95% CI 11·50–13·48) for HBsAg, respectively. The prevalence of anti-HCV and HBsAg varied according to the route of HIV transmission. Compared to those with sexually acquired HIV infection, intravenous drug users and blood donors/recipients had the greatest risk of carrying anti-HCV. Needle sharing and unprotected sexual exposures are important modes of transmission for HBV. Further interventions including health education and harm reduction strategies should be implemented in high-risk populations.
HIV-positive persons and the elderly have increased risk for influenza-related complications, including pneumonia. Using claims data for pneumonia and influenza (P&I) hospitalization in the USA, we described the temporo-demographic trends and in-patient case-fatality in persons aged ⩾65 years by HIV status. Our results showed a near doubling in the fraction of P&I admissions representing HIV-positive persons between 1991 and 2004 [relative risk (RR) 1·95, 95% confidence interval (CI) 1·80–2·13]. HIV-positive adults were younger (70·3 vs. 79·9 years, P<0·001), and had higher case-fatality (18·0% vs. 12·6%, P<0·001). Adjusting for other variables, case-fatality decreased by 5·8% in HIV-positive persons with the availability of highly active antiretroviral therapy (P=0·032). However, HIV-positive seniors were still 51% more likely to die during hospitalization than HIV-negative persons in 2004 (OR 1·51, 95% CI 1·23–1·85). HIV-infected persons represent a growing fraction of the elderly population hospitalized with P&I. Additional measures are needed to reduce case-fatality associated with P&I in this population.
Arboviruses and human viruses associated with animals
Japanese encephalitis (JE) is an important arboviral infection of public health concern. There is a significant variation in mortality (10–30%) in JE viral infection. Epidemics of JE have become regular features in the northen states of India. The recent resurgence of the A226V mutation leading to a widespread Chikungunya epidemic motivated the investigators to search for any such mutational occurrence with Japanese encephalitis virus (JEV) isolated from this region. This study looked for mutation of clinical strains at amino-acid positions 176, 177, 227, 244, 264 and 279. A novel mutation S227T was detected corresponding to the loop region of domain II, E gene of JEV in comparison to Indian and other isolates from different parts of the world. Genotype III was found to be circulating in this geographical area. Further studies are required to ascertain its role in JE pathogenesis and vector competency.
Although high rates of clinical infection with methicillin-resistant Staphylococcus aureus (MRSA) have been reported in HIV-infected adults, data on MRSA colonization are limited. We enrolled HIV-infected adults receiving care at the Atlanta VA Medical Center. Swabs from each participant's nares and groin were cultured with broth enrichment for S. aureus. Of 600 HIV-infected adults, 79 (13%) were colonized with MRSA and 180 (30%) with methicillin-susceptible S. aureus. MRSA pulsed-field gel electrophoresis types USA300 (n=44, 54%) and USA500/Iberian (n=29, 35%) predominated. Inclusion of groin swabs increased MRSA detection by 24% and USA300 detection by 38%. In multivariate analysis, MRSA colonization compared to no MRSA colonization was associated with a history of MRSA clinical infection, rarely or never using condoms, and contact with prisons and jails. In summary, the prevalence of MRSA colonization was high in this study of HIV-infected adults and detection of USA300 was enhanced by groin culture.
Rabies is a prevalent and re-emerging disease in South Africa particularly in rural areas with high human densities. Outbreaks are frequently reported in the north and eastern parts of this country, probably an indication of inadequacy in the control of the disease. Following the 2005/2006 outbreak in Limpopo, we undertook an analysis of case surveillance data and genetically characterized 18 rabies viruses, all recovered from domestic dogs. Although rabies prevalence gradually declined annually from 2007, dog rabies still remains a public and veterinary health hazard in this region. Sylvatic rabies cycles are maintained by the black-backed jackal species in specific ecological conditions in the northwest of the province (Waterberg area), unlike in the north and east (Vhembe and Mopani districts, respectively), where spillover of infection between dogs and jackals is likely to predominate. Genetic analysis demonstrated that the rabies virus strain currently circulating within dog populations in Limpopo province is the same variant responsible for the 2005/2006 rabies outbreak. However, residual foci probably exist hence the observed sporadic outbreaks. These data further underline the value of continuous and sustainable dog immunization in controlling rabies.
Mobility is associated with HIV due to more risky sexual behaviour of mobile groups such as travellers and migrants. Limited participation of such groups may reduce the effectiveness of HIV interventions disproportionally. The established STDSIM model, which simulates transmission and control of HIV and STD, was extended to simulate mobility patterns based on data from Tanzania. We explored the impact of non-participation of mobile groups (travellers and recent migrants) on the effectiveness of two interventions: condom promotion and health education aiming at partner reduction. If mobile groups do not participate, the effectiveness of both interventions could be reduced by 40%. The impact of targeting travellers with a combined HIV campaign is close to that of a general population intervention. In conclusion, it is important to account for possible non-participation of migrants and travellers. If non-participation is substantial, impact of interventions can be greatly improved by actively approaching these people.
Hepatitis E infections in humans are usually acquired in endemic countries in Asia or Africa. In Sweden 17 cases infected in Europe, between 1993 and 2009, were identified. All had clinical hepatitis E with unknown source of infection. Hepatitis E virus (HEV) was identified in faecal samples from 63 piglets in 12 pig farms in Sweden. HEV was also identified in blood from 13 out of 159 investigated Swedish wild boars from nine counties. Partial HEV genomes from humans, pigs and wild boars were sequenced and compared by phylogeny. The results showed close relatedness between HEV strains from piglets from the same farm and from wild boars from the same county. HEV strains from humans showed relatedness with strains from pigs and wild boars from the same county. This study showed that HEV strains form geographical clusters in the phylogenetic tree. The methods used in this study may thus be used for tracing the origin of an infecting strain. Furthermore, this study indicated that there are endemic sources of human HEV infections in Sweden.
A preliminary study was conducted to determine the presence of spotted fever rickettsiae in two species of British tick (Ixodes ricinus and Dermacentor reticulatus). The 16S rRNA gene of Rickettsia spp. was detected in 39/401 (9·7%) of ticks tested, including 22/338 (6·5%) I. ricinus and 17/63 (27%) D. reticulatus. Some positive I. ricinus samples showed 100% homology with Rickettsia helvetica (10/22), and most positive D. reticulatus showed 100% homology with R. raoultii (13/17). Five other Rickettsia spp. were detected exhibiting 96–99% homology. Ticks positive for rickettsiae were collected from various hosts and from vegetation from eight counties across Great Britain. The distribution of R. helvetica in various engorged and unfed stages of I. ricinus suggests that R. helvetica is widespread. R. raoultii was found in questing adult D. reticulatus in Wales and England. This is the first evidence of potentially pathogenic spotted fever rickettsiae in British ticks.
The objective of this study was to investigate risk factors for norovirus-associated infectious intestinal disease (IID) and asymptomatic norovirus infection. Individuals with IID and healthy controls were recruited in a community-based study in England (1993–1996). This is the first risk-factor study to use viral load measurements, generated by real-time RT–PCR, to identify cases of norovirus-associated IID and asymptomatic infections. Using multivariable logistic regression the main risk factor identified for norovirus-associated IID was contact with a person with IID symptoms. Infectious contacts accounted for 54% of norovirus cases in young children and 39% of norovirus cases in older children and adults. For young children, contacts outside the household presented the highest risk; for older children and adults, the highest risk was associated with child contacts inside the household. Foreign travel and consumption of shellfish increased the risk of norovirus-associated IID. Lifestyle and dietary factors were associated with a decreased risk of both norovirus-associated IID and asymptomatic infection. No risk factors were identified for asymptomatic norovirus infection.
In mid-June 2009, an outbreak of pandemic (H1N1) 2009 (pH1N1) infection occurred in a secondary school in Hong Kong. We carried out an epidemiological investigation to delineate the characteristics of the outbreak, gauge the extent of secondary household transmission, and assess the protective role of oseltamivir in household contacts. We interviewed pH1N1-confirmed cases using a standardized questionnaire. Sixty-five of 511 students in the school were affected. Of the 205 household contacts identified, 12 were confirmed as cases. All cases recovered. The estimated secondary household attack rate was 5·9% (95% CI 2·7–9·1). Household contacts aged <18 years were about 15 times more likely to be infected than older contacts. Household contacts who had received oseltamivir prophylaxis were less likely to acquire a secondary infection than those who had not (odds ratio=0). The estimated mean household serial interval of pH1N1 virus was 2·8 days (95% CI 2·1–3·4 days).
Haematopoietic stem cell transplant (HSCT) recipients lose immune memory of exposure to infectious agents and vaccines accumulated throughout their lifetime and therefore need to be revaccinated. We aimed to evaluate the influence of different factors on hepatitis A virus (HAV) immunity in both child and adult HSCT recipients living in an intermediate endemic region, Turkey. Eighty patients (age range 2·5–57 years) who had HAV serology prior to HSCT were evaluated. The prevalence of HAV seropositivity was 85% (n=68) before HSCT. There was no history of HAV vaccination before HSCT in children and HAV vaccine was not available in Turkey 10 years ago, so it was assumed that all seropositive patients reflected natural immunity. After the exclusion of six patients with autologous HSCT, the remaining 62 seropositive and allogeneic patients were included in this retrospective study. The duration of HAV seropositivity was estimated using the Kaplan–Meier method, log-rank analysis and Cox regression models. Estimated mean time to loss of HAV seropositivity was 48·6 months after transplantation. Patients who were older (⩾18 years) at transplantation and who had older (⩾18 years) donors became seronegative later (P<0·05). Cox backward-stepwise regression confirmed that older age of recipient at transplantation was the only significant parameter for HAV seropositivity (P<0·05). HAV-inactivated vaccine might be recommended later to older HSCT recipients in intermediate endemic regions.
The association between coronaviruses and bats is a worldwide phenomenon and bats belonging to genus Rhinolophus are the reservoir host for several coronaviruses, including a large number of viruses closely related genetically to severe acute respiratory syndrome-coronavirus (SARS-CoV). We carried out a survey in colonies of Italian bats (Rhinolophus ferrumequinum) for the presence of coronaviruses. Two of 52 R. ferrumequinum captured from different Italian areas tested positive by reverse transcription–PCR for a fragment of RNA-dependent RNA polymerase (RdRp) gene of viruses related to Coronavirus. Phylogenetic analysis revealed close correlations between one of the positive samples and SARS-related CoV belonging to the genus Betacoronavirus.
An unlinked anonymous survey was conducted to measure the prevalence of selected markers for HIV, hepatitis B and C infection in recruits to the UK Armed Forces to inform future screening and hepatitis B vaccination policies. During 2007, nearly 14 000 left-over samples taken from new recruits for blood typing were collected, unlinked from identifiers and anonymously tested for HIV, hepatitis C and current and past cleared hepatitis B infection. Overall, serological evidence of HIV and hepatitis C was found in 0·06% and 0·06% of recruits, respectively. Evidence of past cleared and current hepatitis B infection was found in 3·63% and 0·37% of recruits, respectively. Overall, prevalence rates were broadly consistent with UK population estimates of infection. However, HIV and hepatitis B prevalence was higher in recruits of African origin than in those from the UK (P<0·0001). Screening for these infections is an option that could be considered for those entering Services from high-prevalence countries.
Antibiotics and antibiotic resistance: veterinary and human
The aims of this study were to determine adherence to the perioperative antibiotic prophylaxis (PAP) protocol used at a large Italian teaching hospital during a 6-year period, to assess the variables associated with inappropriate administration, and to measure the impact on surgical site infection (SSI) rates. There were 28 621 patients surveyed of which 74·6% received PAP. An improvement in adherence to the PAP protocol was registered for 58·8% of patients. Significant risk factors were an American Society of Anesthesiologists (ASA) score ⩾2 [odds ratios (OR) from 1·28 (95% confidence interval (CI) 1·19–1·37) to 1·87 (95% CI 1·43–2·44)], prolonged duration of surgery (OR 1·68, 95% CI 1·56–1·82) and urgent surgery (OR 2·16, 95% CI 1·96–2·37). During the study period, a significant reduction in SSIs rates was detected. We concluded that the global reduction of inadequate PAP administration signifies the efficacy of a multidisciplinary quality improvement initiative on antimicrobial utilization, and this is supported by the observed reduction of the SSI rate.