TT virus infection in nonhuman primates and characterization of the viral genome: identification of simian TT virus isolates

Newly discovered TT virus (TTV) is widely distributed in human populations. To understand more about the relationship between TTV and its hosts, we tested 400 sera from various nonhuman primates for the presence of TTV DNA by PCR assay. We collected serum samples from 24 different species of nonhuman primates. TTV DNA was determined by PCR with primers designed from the 5'-end region of the TTV genome. Nucleotide sequencing and phylogenetic analysis of viral genomes were also performed. TTV DNA was detected in 87 of 98 (89%) chimpanzees and 3 of 21 (14%) crab-eating macaques. Nucleotide sequences of the PCR products obtained from both animals were 80 to 100% identical between two species. In contrast, the sequences differed from TTV isolates in humans by 24 to 33% at the nucleotide level and 36 to 50% at the amino acid level. Phylogenetic analysis demonstrated that all TTV isolates obtained from simians were distinct from the human TTV isolates. Furthermore, TTV in simians, but not in humans, was classified into three different genotypes. Our results indicate that TTV in simians represents a group different from, but closely related to, TTV in humans. From these results, we tentatively named this TTV simian TTV (s-TTV). The existence of the s-TTV will be important in determining the origin, nature, and transmission of human TTV and may provide useful animal models for studies of the infection and pathogenesis of this new DNA virus.     

A serological survey for human immunodeficiency virus types 1 and 2 of individuals who visited health centers in Tokyo

The serum antibodies to human immunodeficiency virus types 1 (HIV-1) and 2 (HIV-2) were examined for among individuals who visited health centers in Tokyo. Of 8,198 sera screened, one was true-positive and 37 false-positive for HIV-1 antibodies. These 37 false-positives and 305 sera from the population groups at risk for HIV-2 (42 sojourners in Africa, 251 homo- and bisexuals, and 19 prostitutes) were further examined for HIV-2 antibodies by indirect immunofluorescence and Western blotting. No antibodies reactive with HIV-2 were detected in the sera examined. Serological cross-reactivity between HIV-1 and HIV-2 was examined by use of rabbit antisera.     

TT virus loads and lymphocyte subpopulations in children with acute respiratory diseases

TT virus (TTV) produces chronic plasma viremia in around 90% of healthy individuals of all ages and has, therefore, been proposed as a commensal human virus. We recently demonstrated that in children hospitalized for acute respiratory diseases high TTV loads were associated with severe forms of disease. Here, we report that in such children TTV loads showed an inverse correlation with the percentage of circulating total T and helper T cells and a direct correlation with the percentage of B cells. Thus, florid TTV replication might contribute to lymphocyte imbalances and, possibly, immunosuppressive effects, thus resembling related animal viruses.     

Randomised controlled trial of routine hospital clinic care versus routine general practice care for type II diabetics.

Two hundred patients with type II diabetes were entered into a randomised controlled trial lasting five years to compare routine care of this condition by a hospital diabetic clinic with routine care in general practice. Fewer patients in the group being cared for by their general practitioner (general practice group) were regularly reviewed or had regular estimations of blood glucose concentration. More patients in the general practice group than in the hospital group were admitted to hospital for medical reasons during the study (25 (24%) compared with 17 (18%] and more patients in the general practice group died (18) than did in the hospital group (6). At the end of the study mean concentrations of haemoglobin A1 were higher in the general practice group (10.4%) than in the hospital group (9.5%). Routine care in general practice for patients with type II diabetes was less satisfactory than care by the hospital diabetic clinic.     

Influences on hospital admission for asthma in south Asian and white adults: qualitative interview study

ObjectiveTo explore reasons for increased risk of hospital admission among south Asian patients with asthma.DesignQualitative interview study using modified critical incident technique and framework analysis.SettingNewham, east London, a deprived area with a large mixed south Asian population.Participants58 south Asian and white adults with asthma (49 admitted to hospital with asthma, 9 not admitted); 17 general practitioners; 5 accident and emergency doctors; 2 out of hours general practitioners; 1 asthma specialist nurse.ResultsSouth Asian and white patients admitted to hospital coped differently with asthma. South Asians described less confidence in controlling their asthma, were unfamiliar with the concept of preventive medication, and often expressed less confidence in their general practitioner. South Asians managed asthma exacerbations with family advocacy, without systematic changes in prophylaxis, and without systemic corticosteroids. Patients describing difficulty accessing primary care during asthma exacerbations were registered with practices with weak strategies for asthma care and were often south Asian. Patients with easy access described care suggesting partnerships with their general practitioner, had better confidence to control asthma, and were registered with practices with well developed asthma strategies that included policies for avoiding hospital admission.ConclusionsThe different ways of coping with asthma exacerbations and accessing care may partly explain the increased risk of hospital admission in south Asian patients. Interventions that increase confidence to control asthma, confidence in the general practitioner, understanding of preventive treatment, and use of systemic corticosteroids in exacerbations may reduce hospital admissions. Development of more sophisticated asthma strategies by practices with better access and partnerships with patients may also achieve this.

What is already known on this topic

South Asian patients with asthma are at increased risk of hospital admission with asthma compared with white patientsNo consistent differences in severity or prevalence of asthma, prescribed drugs, or asthma education have been described, and interventions to reduce admission rates in Asian patients have met with variable success

What this study adds

Compared with white patients, south Asian patients admitted to hospital with asthma had less confidence to control asthma, were unfamiliar with the concept of preventive medication, and had less confidence in their general practitionersSouth Asian patients managed asthma attacks through family advocacy and without systematic changes in prophylaxis and without systemic corticosteroidsPatients reporting difficulty in accessing primary care during attacks were often south Asian     

Relationships between TT virus infection and hepatitis C virus response to interferon therapy in doubly infected patients

A group of 24 well-characterized patients doubly infected with hepatitis C virus (HCV) and TT virus (TTV) were studied to evaluate whether the loads and number or identity of the genogroups of TTV they carried could affect the response of HCV infection to interferon-alpha (IFN) treatment. The features of HCV infection in the study patients provided a fair representation of the variables that are usually found in considering patients for IFN treatment. The same was true for the features of TTV infection. In particular, plasma loads of TTV varied over a wide range in individual patients, and infection with multiple TTV genogroups was extremely frequent. TTV genogroups 1 and 3 were the most prevalent, followed by genogroups 4 and 5. The HCV response to IFN was evaluated by measuring plasma viraemia at 24 hours and 30 days after initiation of treatment. The results showed that the TTV parameters investigated had little or no impact on the response of HCV to therapy. Due to study design, these results do not exclude that the presence of a concomitant TTV infection can affect how HCV infection responds to treatment. However, they indicate that, should such effects exist, they would be independent on load and genetic features of the infecting TTV.     

Admissions to hospital of children with sickle-cell anaemia: a study in south London.

Admissions to hospital of 171 children with sickle-cell anaemia, genotype Hb SS, were reviewed over a 20-year period. Altogether 887 admissions occurred in 797 patient-years. The commonest cause of admission was painful vaso-occlusive crisis. Appreciable morbidity also resulted from pulmonary disease, infection, and anaemic episodes. The complications resulting in the most severe illness were acute splenic sequestration, pneumococcal meningitis, and some episodes of erythroid hypoplasia resulting in very low haemoglobin concentrations. Most deaths occurred in children aged under 5. Mortality and morbidity could be reduced by measures including prophylaxis of pneumococcal infections and more active treatment of seemingly minor illness in children with sickle-cell anaemia.     

Multiple infection of TT virus (TTV) with different genotypes in Japanese hemophiliacs

To clarify the persistent TT virus (TTV) infection, we studied a possibility of multiple TTV infection by genotype analysis of isolated TTV obtained from seven Japanese hemophiliacs. The nucleotide sequences including 222 bp in the open reading frame 1 (ORF1) region of 10 TTV isolates from each patient were analyzed and classified into various TTV genotypes such as G1 to G6 by phylogenetic analysis using a N-J method. Multiple TTV genotypes were observed in all the hemophiliacs: three different TTV genotypes were found in three patients, whereas four different TTV genotypes were observed in the other three patients. The remaining patient was also infected with TTV of five different genotypes. Moreover, new TTV genotypes were found in these seven patients and tentatively designated as G7. The present findings indicate that multiple TTV infection with different TTV genotypes has occurred in Japanese hemophiliacs. They also provide valuable information to understand persistent TTV infection.     

End of life care in HIV-infected children who died in hospital

The aim of this study was to evaluate terminal care among hospitalized children who died of HIV/AIDS. The design was a retrospective chart review of the terminal hospitalization. The setting was a public, secondary and tertiary children's hospital in Cape Town, South Africa (SA). The patients included a consecutive series of in-patient deaths from HIV-related causes. The main outcome measures included: documentation of do not resuscitate (DNR) orders and comfort care plans, intensity of diagnostic and therapeutic interventions in last 24 hours of life, and presence of pain and distress in last 48 hours of life. The results are based on the review of 165 out of 167 in-patient deaths. Of those, 79% of patients died in general wards. Median age and length of stay were 4 months and 6 days respectively. A total of 84% of patients had a DNR order. DNR orders appeared simultaneously in only 41% of medical and nursing notes. Only 44% of patients had a comfort care plan. Pain and distress in the last 48 hours was documented in 55% of patients who died in the general wards. Respiratory symptomatology and painful skin conditions accounted for most discomfort. Half (36/72) the patients with pain and distress, including 16 with a comfort care plan, received no analgesia. Conclusions drawn found that, despite clinical uncertainty, doctors made tough end of life decisions that included DNR orders and comfort care plans. The lower rate of comfort care plans suggests doctors had difficulty making the transition from curative to palliative care. Many comfort care plans were incoherent and included interventions unlikely to promote patients' comfort. In light of the HIV/AIDS pandemic in SA, reforms are needed to integrate palliative care within mainstream hospital medicine. However, without adequate human resources including trained interpreters, doctors and nurses will struggle to deliver optimal terminal care in acute hospitals.     

Analysis of the results of serum studies of children and adults for antibodies to the poliomyelitis virus in a multiyear effort at vaccinal prevention of this infection

The results of testing the blood sera of children and adults for the presence of antibodies to poliomyelitis have shown the low level of immunity to this infection. The authors believe that the main reasons of the tendency towards the decrease in immunity to poliomyelitis, observed in recent years, are the drawbacks of the vaccinal prevention of this infection and the absence of a differentiated approach to the choice of immunization methods under concrete conditions. Mass immunization against poliomyelitis is recommended, especially in the southern and south-eastern regions of the U.S.S.R.     

Acute diarrhoea in a community cohort of children who received an oral rotavirus vaccine in Northeast Brazil

Rotavirus is an important cause of childhood diarrhoea. A monovalent rotavirus vaccine (Rotarix?) was introduced into the Immunization Program of Brazil in 2006. In this study, we describe the incidence and burden of disease of rotavirus diarrhoea in two cohorts of children (vaccinated and unvaccinated). We followed two groups of 250 children under one year old, who were enrolled in December 2006 from a low-income residential area in Northeast Brazil. The children were monitored every two weeks for two years. Stool samples from children with diarrhoea were examined for the presence of rotavirus. Rotaviruses were genotyped using real time-polymerase chain reaction. The mean numbers of all-cause diarrhoea episodes/child (adjusted for age) in the first year were 0.87 and 0.84, in vaccinated and unvaccinated children, respectively. During the second year, the number of episodes/child decreased to 0.52 and 0.42. Only 16 (4.9%) of 330 stool samples were rotavirus-positive (10 vaccinated and 6 unvaccinated children) and only P[4]G2 rotaviruses were identified. All-cause diarrhoea episodes were more severe in unvaccinated children in the first year of age (p < 0.05), while vaccinated children had more severe episodes 18 months after vaccination. Rotavirus diarrhoea incidence was very low in both groups.     

Detection of TT virus among chimpanzees in the wild using a noninvasive technique

Zoonotic transmission and emergence of pathogens are serious threats to endangered populations of free-ranging primate species. Recent discovery of a nonpathogenic yet highly prevalent virus in human populations, TT virus (TTV), has prompted studies into the presence of this virus among captive individuals of other species of nonhuman primates. In this study, we screened captive primate species for TTV. In addition, we provide the first data on TTV infectionin free-ranging primates by noninvasive screening of three chimpanzee (Pan troglodytes sweinfurthii) commlunities. Phylogenetic relationships between virus isolates and those previously reported from hulman popullations, captive primates, and domesticated species are inferred. Our findings are discussed with respect to potential zoonotic events that may result from increased levels of human encroachlment into wild habitats.     

Modified enzymatic procedure for the routine determination of glycerol and triglycerides in plasma

A modification of Wieland's enzymatic procedure for glycerol analysis is presented. It is simple and precise, and readily applicable to the routine analysis of plasma and tissue glycerol and triglycerides. Optimal precision is obtained in samples containing 0.003-0.400 micromole of glycerol per ml, which in this method is equivalent to plasma levels of 0.011 to 1.40 micromoles/ml.     

Helicobacter pylori infection in children and adults: a single pathogen but a different pathology

Background. The aims of this retrospective study were to ascertain in large series of children and adults: the relationship of the infecting strain to gastric mucosal lesions; and the relationship of the infecting strain to its duodenal localization. Materials and Methods. We studied 307 and 604 consecutive children and adults. In gastric mucosal samples H. pylori was cultured, genotyped and histologically assessed, while inflammation, activity and intestinal metaplasia were graded. In a subset of 171 patients H. pylori ureaseA (ureA) and cagA genes were amplified (PCR) using mucosal biopsies from the duodenum. Results. H. pylori infection was diagnosed in 40 children and 308 adults. cagA was identified in 50% and 65.5% of infected children and adults. Antral activity was associated with the density of infecting bacteria (p < .001) and with cagA (p < .01). Intestinal metaplasia was correlated with cagA (p < .001). The ureA gene was found in 56 duodenal samples from 82 H. pylori positive patients. Duodenal H. pylori ureA was significantly more frequent in patients with duodenal diseases than in those without (p < .01), cagA positive strains being mainly involved in the infection of this anatomical area (p < .01). Conclusions. A severe H. pylori‐associated gastritis is more prevalent when the density of infecting bacteria is high and when cagA positive strains cause the infection. The most virulent cagA positive H. pylori colonizes not only the gastric, but also the duodenal mucosa, which can be directly damaged by the bacteria itself or by its products.     

TT virus in the nasal secretions of children with acute respiratory diseases: relations to viremia and disease severity

The natural history and pathogenic potential of the recently identified TT virus (TTV) are currently a matter of intensive investigation. In an attempt to shed some light on these issues, nasal and blood specimens of 1- to 24-month-old children hospitalized with a clinical diagnosis of acute respiratory disease (ARD) were examined for the presence, load, and genetic characteristics of TTV. The results have indicated that at least in young children, the respiratory tract not only represents a route by which abundant TTV can be shed into the environment but also may be a site of primary infection and continual replication. Although we found no compelling evidence that TTV was the direct cause of ARD in some of the children studied, the average loads of TTV were considerably higher in patients with bronchopneumonia (BP) than in those with milder ARD, raising interesting questions about the pathophysiological significance of TTV at this site. Furthermore, group 4 TTV was detected almost exclusively in children with BP.     

Circular double-stranded forms of TT virus DNA in the liver

TT virus (TTV) is an unenveloped, circular, and single-stranded DNA virus commonly infecting human beings worldwide. TTV DNAs in paired serum and liver tissues from three viremic individuals were separated by gel electrophoresis and characterized biophysically. TTV DNAs in sera migrated in sizes ranging from 2.0 to 2.5 kb. TTV DNAs in liver tissues, however, migrated at 2.0 to 2.5 kb as well as at 3.5 to 6.1 kb. Both faster- and slower-migrating forms of TTV DNAs in the liver were found to be circular and of the full genomic length of 3.8 kb. TTV DNAs migrating at 2.0 to 2.5 kb, from either serum or liver tissues, were sensitive to S1 nuclease but resistant to restriction endonucleases, and therefore, they were single-stranded. By contrast, TTV DNAs in liver tissues that migrated at 3.5 to 6.1 kb were resistant to S1 nuclease. They migrated at 3.7 to 4.0 kb after digestion with EcoRI, which suggests that they represent circular, double-stranded replicative intermediates of TTV. When TTV DNAs were subjected to strand-specific primer extension and then amplified by PCR with internal primers, those in serum were found to be minus-stranded DNAs while those in liver tissues were found to be a mixture of plus- and minus-stranded DNAs. These results suggest that TTV replicates in the liver via a circular double-stranded DNA.