Results of microbiological tests for 1451 Indigenous Adults admitted 2005–2010^a.

<p>^a Pair-wise comparisons of Strongyloides serological results were Bonferroni-corrected.</p><p>Abbreviations: HBV, hepatitis B virus; anti-HBc, hepatitis B core antibody positive; HBeAg, hepatitis B e antigen positive; HBsAg, hepatitis B surface antigen positive; WB, Western blot.</p

Map of the study area in central Australia including HTLV-1 seropositivity rates for 952 Indigenous adult residents of remote communities divided by quadrant according to their residence relative to the regional center of Alice Springs (green circle).

<p>Number of residents tested: North, 335; East, 69; South, 241; West, 307. Abbreviations: NT, Northern Territory of Australia; QLD, Queensland; SA, South Australia; WA, West Australia. Scale bar = 250 km.</p

Adjusted Poisson modeling of predictors of HTLV-1 infection.

<p>^a Residence in remote communities relative to the regional center of Alice Springs.</p><p>^b Patients for whom an ICD-10 AM discharge morbidity code of bronchiectasis was recorded and where this was confirmed by HRCT.</p><p>^c Conditions identified from discharge morbidity codes.</p><p>^d Excluding hematological malignancies.</p><p>^e Strongyloides identified by ICD-10 AM code.</p><p>^f Blood stream infections identified from blood cultures. Enteric pathogens, Enterobacteriaceae other than <i>Escherichia coli</i>; skin pathogens, <i>Staphylococcus aureas</i> and <i>Streptococcus pyogenes</i>; respiratory pathogens, <i>Streptococcus pneumoniae</i> and <i>Haemophilus influenzae</i>.</p><p>Abbreviations: BSI, blood stream infection; HBsAg, Hepatitis B surface antigen positive.</p

Adjusted Cox proportional hazards modeling of predictors of death^a.

<p>^a Including 338 deaths that occurred after 1^st January 2005.</p><p>^b Risk of death for each 5 years increase in age.</p><p>^c Excluding 134 patients who resided outside central Australia and 2 patients whose place of residence was unknown.</p><p>^d Identified by ICD-10 AM coding.</p><p>^e Definite bronchiectasis identified by ICD-10 AM code and confirmed by High Resolution Computed Tomography.</p><p>^f Strongyloides identified by ICD-10 AM code.</p><p>^g Blood stream infections identified from blood cultures.</p><p>^h Excluding <i>Escherichia coli</i>.</p><p>Abbreviations: HBsAg, hepatitis B surface antigen; HTLV-1, Human T-Lymphotropic Virus type 1.</p

Lytic Gene Expression Is Frequent in HSV-1 Latent Infection and Correlates with the Engagement of a Cell-Intrinsic Transcriptional Response

<div><p>Herpes simplex viruses (HSV) are significant human pathogens that provide one of the best-described examples of viral latency and reactivation. HSV latency occurs in sensory neurons, being characterized by the absence of virus replication and only fragmentary evidence of protein production. In mouse models, HSV latency is especially stable but the detection of some lytic gene transcription and the ongoing presence of activated immune cells in latent ganglia have been used to suggest that this state is not entirely quiescent. Alternatively, these findings can be interpreted as signs of a low, but constant level of abortive reactivation punctuating otherwise silent latency. Using single cell analysis of transcription in mouse dorsal root ganglia, we reveal that HSV-1 latency is highly dynamic in the majority of neurons. Specifically, transcription from areas of the HSV genome associated with at least one viral lytic gene occurs in nearly two thirds of latently-infected neurons and more than half of these have RNA from more than one lytic gene locus. Further, bioinformatics analyses of host transcription showed that progressive appearance of these lytic transcripts correlated with alterations in expression of cellular genes. These data show for the first time that transcription consistent with lytic gene expression is a frequent event, taking place in the majority of HSV latently-infected neurons. Furthermore, this transcription is of biological significance in that it influences host gene expression. We suggest that the maintenance of HSV latency involves an active host response to frequent viral activity.</p></div

Associations between baseline characteristics and time to virological failure.

<p>*per category; EFV, efavirenz; NVP, nevirapine.</p><p>schoenfelds p = 0.12.</p

Patient characteristics for 1451 Indigenous Adults admitted 2005–2010^a.

<p>^a Excluding patients with an indeterminate western blot and those who died prior to 2005.</p><p>^b Analyzed according to gender within each group.</p><p>^c Excluding 134 patients who resided outside central Australia and 2 patients whose place of residence was unknown. Data are expressed as proportion of total patients tested for each place of residence.</p><p>^d Residents of remote communities relative to the regional center of Alice Springs and excluding 498 Alice Springs residents. Data are expressed as proportion of total patients tested for each quadrant.</p><p>^e Died during observation period.</p><p>^f All pair-wise quadrant comparisons were p<0.001 (Bonferroni-corrected), except the North vs East comparison.</p><p>^g Pair-wise comparisons of urban-residence compared with all other residences were p<0.001 (Bonferroni-corrected).</p

Comparison of clinical conditions identified by International Classification of Diseases-10 (Australian Modification) morbidity codes according to HTLV-1 serostatus among 1451 Indigenous adults admitted 2005–2010^a.

<p>Data derived from 115,919 admissions (HTLV-1 seropositive 39,967; HTLV-1 seronegative, 75,952) among 481 HTLV-1 seropositive and 856 HTLV-1 seronegative Indigenous adults.</p><p>^a Excluding patients with an indeterminate western blot and those who died prior to 2005.</p><p>^b Non-hematological malignancies.</p><p>^c LRTI other than pneumonia.</p><p>^d Bronchiectasis confirmed by chest high resolution computed tomography.</p><p>^e Identified by ICD-10 AM coding.</p><p>^f Probable HAM/TSP. Confirmatory tests not applied to cerebrospinal fluid.</p><p>no p-value provided due to small numbers recorded.</p><p>Abbreviations: ATLL, adult T cell leukemia/lymphoma; CCF, congestive cardiac failure; CKD, chronic kidney disease; CLD, chronic liver disease; HAM/TSP, HTLV-1 associated myelopathy/tropical spastic paraparesis; HD, hemodialysis; LRTI, lower respiratory tract infection; WB, Western blot.</p

Admission rates for respiratory conditions and other infections according to HTLV-1 serostatus.

<p>Admission rates for 1317 adult Indigenous residents of central Australia 2005–2010 admitted to Alice Springs Hospital with respiratory conditions and infections. Excluding patients who died prior to 2005 and those residing outside central Australia for whom admission data was incomplete.</p><p>^a Identified by ICD-10 AM code. Bronchiectasis was confirmed by chest high resolution computed tomography.</p><p>^b LRTI other than pneumonia.</p><p>^c Identified by ICD-10 AM coding with the exception of BSI episodes.</p><p>^d The number of blood cultures that yielded a significant pathogen as defined in <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002643#s2" target="_blank">methods</a>.</p><p>Abbreviations: BSI, blood stream infection; COPD, chronic obstructive pulmonary disease; LRTI, lower respiratory tract infection.</p

Cumulative hazard estimate for virological failure.

<p>Cumulative hazard estimate for virological failure.</p