Univariate and multivariate analyses of factors associated with HHV-8 oral shedding and viremia.

<p>Abbreviations: IRR = incidence rate ratio, CI = confidence interval, vs = versus.</p>A<p>Calculated for HIV seropositive participants only.</p>B<p>Multivariate model, adjusted for other variables indicated in table.</p>C<p>Data missing for 2 participants.</p

Rate of HHV-8 detection from oral swabs and plasma samples in individual participants, by HIV and KS status.

<p>Participants are numbered in ascending order according to oral shedding rate in each group. The participants collected a median of 29 oral swabs, 4 genital swabs, and 5 plasma samples per person.</p

Enrollment and follow-up of participants in HHV-8 replication study.

<p>Enrollment and follow-up of participants in HHV-8 replication study.</p

Frequency and Quantity of HHV-8 Detection among Participants with and without HIV and KS.

*<p>Among positive samples.</p>a<p>P-value refers to comparison between KS negative and KS positive persons, using chi-square test.</p>b<p>P-value refers to comparison between KS negative and KS positive persons, using GEE Poisson regression.</p>c<p>P-value refers to comparison between HIV+/KS+ persons compared to the other groups, using GEE Gaussian regression.</p>d<p>P-value refers to comparison between HIV positive and HIV negative persons, using GEE Poisson regression.</p>e<p>Missing for 1 HIV+/KS+ participant.</p>f<p>Missing for 2 HIV+/KS+, 2 KS+/HIV−, and 1 KS−/HIV− participants.</p>g<p>Only 1 positive swab collected.</p

Demographic, clinical and behavioral characteristics of participants.

<p>All values are n (%) unless otherwise indicated.</p><p>Rows in bold indicate p-value<0.05, for comparison between KS positive and KS negative persons, unless otherwise stated. P-values were calculated using chi-square, Fisher's exact, or Kruskal-Wallis tests, when appropriate.</p>*<p>p-value<0.05 for comparison between HIV positive and HIV negative persons, calculated using chi-square or Kruskal-Wallis test.</p>A<p>Measured for HIV positive participants only.</p>B<p>Data missing for 2 participants (1 HIV negative/KS positive, 1 HIV positive/KS positive).</p>C<p>Only KS positive participants (n = 42) included in denominator.</p>D<p>Data missing for 2 participants.</p

Proportion of participants with HHV-8 detected, by anatomic site and HIV and KS status.

<p>Percentage of participants with HHV-8 detected from oral swabs, genital swabs, or plasma samples. Participants collected a median of 29 oral swabs, 4 genital swabs, and 5 plasma samples. *p<0.05 for the comparison of the proportion of KS positive to KS negative participants with detectable HHV-8, using chi-square test.</p

Study profile: Of the 427 participants screened, 425 were enrolled and started on ART at the three sites.

<p>Three hundred and twenty one participants completed their 12 months visit and had viral load results available at baseline and month 12. Forty nine had viral loads equal or above 1000 copies/ml and were genotyped. Of these 35 participants had HIV drug resistance mutations.</p

Seasonal Pulses of Marburg Virus Circulation in Juvenile <em>Rousettus aegyptiacus</em> Bats Coincide with Periods of Increased Risk of Human Infection

<div><p>Marburg virus (family <em>Filoviridae</em>) causes sporadic outbreaks of severe hemorrhagic disease in sub-Saharan Africa. Bats have been implicated as likely natural reservoir hosts based most recently on an investigation of cases among miners infected in 2007 at the Kitaka mine, Uganda, which contained a large population of Marburg virus-infected <em>Rousettus aegyptiacus</em> fruit bats. Described here is an ecologic investigation of Python Cave, Uganda, where an American and a Dutch tourist acquired Marburg virus infection in December 2007 and July 2008. More than 40,000 <em>R. aegyptiacus</em> were found in the cave and were the sole bat species present. Between August 2008 and November 2009, 1,622 bats were captured and tested for Marburg virus. Q-RT-PCR analysis of bat liver/spleen tissues indicated ∼2.5% of the bats were actively infected, seven of which yielded Marburg virus isolates. Moreover, Q-RT-PCR-positive lung, kidney, colon and reproductive tissues were found, consistent with potential for oral, urine, fecal or sexual transmission. The combined data for <em>R. aegyptiacus</em> tested from Python Cave and Kitaka mine indicate low level horizontal transmission throughout the year. However, Q-RT-PCR data show distinct pulses of virus infection in older juvenile bats (∼six months of age) that temporarily coincide with the peak twice-yearly birthing seasons. Retrospective analysis of historical human infections suspected to have been the result of discrete spillover events directly from nature found 83% (54/65) events occurred during these seasonal pulses in virus circulation, perhaps demonstrating periods of increased risk of human infection. The discovery of two tags at Python Cave from bats marked at Kitaka mine, together with the close genetic linkages evident between viruses detected in geographically distant locations, are consistent with <em>R. aegyptiacus</em> bats existing as a large meta-population with associated virus circulation over broad geographic ranges. These findings provide a basis for developing Marburg hemorrhagic fever risk reduction strategies.</p> </div

Increases in seasonal risk to human health.

<p>Historical spillover events (colored circles on X axis) compared to predicted seasonal levels of PCR+ juveniles (sinusoidal curve). The amplitude of the curve is based on average PCR+ juveniles experimentally determined during birthing (12.4%) and breeding (2.7%) seasons. Large light green vertical rectangles represent the proposed approximate three month seasons of increased risk based on the average level of juvenile infected bats at peak times of encompassing birthing (February and August) and breeding (May and November). Large gray arrows depict the twice yearly influx of newly autonomous juvenile bats born in the prior birthing season. The influx begins at the approximate time of the juvenile's independence from their mothers.</p

Bayesian phylogeny of full length Marburg genome.

<p>Phylogenetic results from a Bayesian analysis on full-length Marburg virus genome sequences from 12 Marburg bat isolates, 3 recent Ugandan human isolates from the two Kitaka miners (01Uga 2007, 02Uga 2007), and the Dutch tourist (01Uga/Net 2008), as well as 45 historical isolates (<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002877#ppat.1002877.s002" target="_blank">Table S2</a> for GenBank accession numbers). Posterior probabilities above .50 are shown above the appropriate nodes. Marburg virus sequences from human cases from Kitaka mine (Uganda 2007) in are in orange, sequences from human cases from Python Cave (2008 Uganda) are in blue, sequences from Kitaka Mine bats are in red, and sequences from Python Cave bats are in green.</p