Clinical epidemiology of bocavirus, rhinovirus, two polyomaviruses and four coronaviruses in HIV-infected and HIV-uninfected South African children

Advances in molecular diagnostics have implicated newly-discovered respiratory viruses in the pathogenesis of pneumonia. We aimed to determine the prevalence and clinical characteristics of human bocavirus (hBoV), human rhinovirus (hRV), polyomavirus-WU (WUPyV) and -KI (KIPyV) and human coronaviruses (CoV)-OC43, -NL63, -HKU1 and -229E among children hospitalized with lower respiratory tract infections (LRTI).Multiplex real-time reverse-transcriptase polymerase chain reaction was undertaken on archived nasopharyngeal aspirates from HIV-infected and -uninfected children (<2 years age) hospitalized for LRTI, who had been previously investigated for respiratory syncytial virus, human metapneumovirus, parainfluenza I-III, adenovirus and influenza A/B.At least one of these viruses were identified in 274 (53.0%) of 517 and in 509 (54.0%) of 943 LRTI-episodes in HIV-infected and -uninfected children, respectively. Human rhinovirus was the most prevalent in HIV-infected (31.7%) and -uninfected children (32.0%), followed by CoV-OC43 (12.2%) and hBoV (9.5%) in HIV-infected; and by hBoV (13.3%) and WUPyV (11.9%) in HIV-uninfected children. Polyomavirus-KI (8.9% vs. 4.8%; p = 0.002) and CoV-OC43 (12.2% vs. 3.6%; p<0.001) were more prevalent in HIV-infected than -uninfected children. Combined with previously-tested viruses, respiratory viruses were identified in 60.9% of HIV-infected and 78.3% of HIV-uninfected children. The newly tested viruses were detected at high frequency in association with other respiratory viruses, including previously-investigated viruses (22.8% in HIV-infected and 28.5% in HIV-uninfected children).We established that combined with previously-investigated viruses, at least one respiratory virus was identified in the majority of HIV-infected and HIV-uninfected children hospitalized for LRTI. The high frequency of viral co-infections illustrates the complexities in attributing causality to specific viruses in the aetiology of LRTI and may indicate a synergetic role of viral co-infections in the pathogenesis of childhood LRTI

Demographic, clinical and laboratory features of children hospitalized for lower respiratory tract infection and in whom samples were available for the current study.

<p>In parenthesis percent of number studied, unless otherwise indicated.</p>1<p>: Chi-square or Fischer test and two-tailed Student t-test or Mann-Whitney test comparing HIV groups.</p>2<p>: Chi-square or Fischer test and two-tailed Student t-test or Mann-Whitney test comparing 9-valent pneumococcal conjugated vaccine (PCV9) and placebo arms.</p>3<p>Gender: HIV-infected overall female vs. male: 45.1% vs. 54.9%, p = 0.001; HIV-infected PCV9 female vs. male: 41.0% vs. 59.1%, p<0.001; HIV-infected placebo female vs. male: 48.4% vs. 51.6%, p = 0.451; HIV-uninfected overall female vs. male: 41.5% vs. 58.5%, p<0.001; HIV-uninfected PCV9 female vs. male: 38.8% vs. 61.2%, p<0.001; HIV-uninfected placebo female vs. male: 44.1% vs. 55.9%, p<0.001.</p>4<p>Axillary temperature: 813 patients with available information; HIV-infected 286; HIV-uninfected 527.</p>5<p>Fever: 1451 patients with available information; HIV-infected 513; HIV-uninfected 938.</p>6<p>Vomit: 1455 patients with available information; HIV-infected 514; HIV-uninfected 941.</p>7<p>Seizures: 1447 patients with available information; HIV-infected 511; HIV-uninfected 936.</p>8<p>Cyanosis: 1454 patients with available information; HIV-infected 513; HIV-uninfected 941.</p>9<p>Oxygen saturation: 1441 patients with available information; HIV-infected 506; HIV-uninfected 935.</p>10<p>Respiratory rate: 1446 patients with available information; HIV-infected 515; HIV-uninfected 930.</p>11<p>World Health Organization (WHO) severe pneumonia definition: 904 patients with available information; HIV-infected 336; HIV-uninfected 568.</p>12<p>Wheezing: 1458 patients with available information; HIV-infected 517; HIV-uninfected 941.</p>13<p>Mechanical ventilation: 1439 patients with available information; HIV-infected 509; HIV-uninfected 930. At the time of the study it was current practice not to offer ventilation to severe AIDS patients.</p>14<p>Alveolar consolidation on chest x-ray (AC-CXR): 1285 patients with available information; HIV-infected 438; HIV-uninfected 847.</p>15<p>C-reactive protein (CRP): 1035 patients with available information; HIV-infected 411; HIV-uninfected 624.</p>16<p>Procalcitonin (PCT): 865 patients with available information; HIV-infected 310; HIV-uninfected 555.</p>17<p>White cell count (WCC): 209 patients with available information; HIV-infected 95; HIV-uninfected 114.</p>18<p>Bacteria infections: overall 1367 patients had blood specimens available for culture, 486 HIV-infected and 881 HIV-uninfected. Bacteria isolated from HIV-infected children included: <i>Streptococcus pneumoniae</i> (n = 16), <i>Escherichia coli</i> (n = 9), <i>Salmonella</i> sp (n = 5), <i>Streptococcus viridans</i> (n = 2), <i>Haemophilus influenzae</i> type b (n = 1), <i>Pseudomonas aeruginosa</i> (n = 1), <i>Haemophilus parainfluenzae</i> (n = 1), <i>Citrobacter freundii</i> (n = 1), <i>Staphylococcus aureus</i> (n = 1) and other <i>Streptococcus</i> (n = 1). Bacteria isolated from HIV-uninfected children included: <i>Streptococcus pneumoniae</i> (n = 8), <i>Haemophilus influenzae</i> type b (n = 3), <i>Streptococcus</i> viridans (n = 3), <i>Escherichia coli</i> (n = 2), <i>Klebsiella</i> sp. (n = 2), <i>Salmonella</i> sp (n = 1), <i>Streptococcus agalactiae</i> (n = 1), <i>Staphylococcus aureus</i> (n = 1), <i>Enterococcus faecalis</i> (n = 1), <i>Micrococcus</i> (n = 1) and <i>Neisseria meningitidis</i> (n = 1). Further 64 (62.7% of all bacteria isolated) and 107 (81.7% of all bacteria isolated) contaminants were cultured in HIV-infected and -uninfected children, respectively.</p

Viral prevalence of newly- or previously-tested viruses according to HIV status.

1<p>: Adjusted odds ratio (aOR) adjusted for age, year of sampling, detection of viruses previously-tested and whether received 9-valent pneumococcal conjugate vaccine or placebo.</p>2<p>: p-value not adjusted.</p>3<p>: Previously-tested by immunofluorescence assay.</p>4<p>: Previously-tested by nested PCR.</p>5<p>: Including viruses previously-tested by immunofluorescence assay (RSV, Influenza A, PIV I–III and adenovirus) and nested-PCR (hMPV).</p>6<p>: All multiple infections included at least one newly-tested virus except in 2 HIV-uninfected children. Viral co-infections with at least one newly-tested virus in HIV-infected children 118 (22.8%) and in HIV-uninfected children 269 (28.5%).</p>7<p>: Not adjusted for detection of viruses previously-tested.</p>8<p>: Single infections with a newly-tested virus no other virus, newly- or previously-tested, was detected.</p><p>OR: odds ratio.</p><p>hBoV: human bocavirus.</p><p>WUPyV: polyomavirus-WU.</p><p>KIPyV: polyomavirus-KI.</p><p>CoV-NL63: coronavirus NL63.</p><p>CoV-HKU1: coronavirus HKU1.</p><p>CoV-OC43: coronavirus OC43.</p><p>CoV-229E: coronavirus 229E.</p><p>hRV: human rhinovirus.</p><p>RSV: respiratory syncytial virus.</p><p>PIV: parainfluenza viruses.</p><p>hMPV: human metapneumovirus.</p

Clinical and laboratory features of HIV-infected and -uninfected children hospitalized for lower respiratory tract infection by detection of viral co-infections.

<p>Viral detection including newly-tested and previously-tested viruses.</p>1<p>: Adjusted odds ratio (aOR) adjusted for age, year of sampling and whether received 9-valent pneumococcal conjugate vaccine or placebo.</p>2<p>: p-value not adjusted.</p><p>OR: odds ratio.</p><p>CRP: C-reactive protein.</p><p>PCT: Procalcitonin.</p><p>CXR-AC: Alveolar consolidation on chest x-ray.</p

Respiratory viruses co-infections in HIV-infected children hospitalized with lower respiratory tract infections.

1<p>: Numbers in parenthesis are percentage of total nasopharyngeal aspirates.</p>2<p>: Only one virus detected. Numbers in parenthesis are percentage of positive samples for that virus.</p>3<p>: Numbers in parenthesis are percentage of samples positive for the specific virus in the column co-infected with the virus(es) in the rows.</p>4<p>: Previously-tested by immunofluorescence assay.</p>5<p>: Previously-tested previously by nested-PCR.</p>6<p>: Including viruses previously-tested by immunofluorescence assay (Influenza A, RSV, PIV, adenovirus) and nested-PCR (hMPV).</p>7<p>: 487 patients had specimens available for culture. Bacteria isolated included: hBoV with <i>Escherichia coli</i> (n = 2) and <i>Salmonella</i> sp (n = 1); WUPyV with <i>Streptococcus pneumoniae</i> (n = 2) and <i>Escherichia coli</i> (n = 1); KIPyV with <i>Streptococcus pneumoniae</i> (n = 3), <i>Escherichia coli</i> (n = 3) and <i>Haemophilus parainfluenzae</i> (n = 1); CoV-NL63 with <i>Streptococcus pneumoniae</i> (n = 2); CoV-OC43 with <i>Escherichia coli</i> (n = 3), <i>Salmonella</i> sp (n = 1), <i>Streptococcus viridans</i> (n = 1) and other <i>Streptococcus</i> (n = 1); hRV with <i>Streptococcus pneumoniae</i> (n = 6), <i>Escherichia coli</i> (n = 3), <i>Streptococcus viridans</i> (n = 1) and <i>Citrobacter freundii</i> (n = 1); hMPV with <i>Salmonella</i> sp (n = 2); PIV with <i>Streptococcus viridans</i> (n = 1); Influenza A with <i>Streptococcus pneumoniae</i> (n = 1) and <i>Escherichia coli</i> (n = 1); Adenovirus with <i>Pseudomonas aeruginosa</i> (n = 1).</p><p>hBoV: human bocavirus.</p><p>WUPyV: polyomavirus-WU.</p><p>KIPyV: polyomavirus-KI.</p><p>CoV-NL63: coronavirus NL63.</p><p>CoV-HKU1: coronavirus HKU1.</p><p>CoV-OC43: coronavirus OC43.</p><p>CoV-229E: coronavirus 229E.</p><p>hRV: human rhinovirus.</p><p>RSV: respiratory syncytial virus.</p><p>PIV: parainfluenza viruses.</p><p>hMPV: human metapneumovirus.</p

Number of specimens analysed in the current study and total specimens collected.

1<p>: Chi-square test comparing 9-valent pneumococcal conjugated vaccine (PCV9) and placebo arms.</p>2<p>: From the full database: patients <2 years old, with diagnosis of lower respiratory tract infections, hospitalized between 1 February 2000 and 31 January 2002, only 1 visit per patient within 28 days.</p

\u3ci\u3eDrosophila\u3c/i\u3e Muller F Elements Maintain a Distinct Set of Genomic Properties Over 40 Million Years of Evolution

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25–50%) than euchromatic reference regions (3–11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11–27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4–3.6 vs. 8.4–8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu