Norovirus shedding among food and healthcare workers exposed to the virus in outbreak settings

BackgroundNoroviruses (NoV) are highly contagious and the leading cause of nonbacterial outbreaks of gastroenteritis worldwide. Individuals who are infected asymptomatically may act as reservoirs and facilitate the transmission of NoV, but the likelihood of workers of becoming infected in outbreak settings has not been systematically studied.ObjectivesWe evaluated the occurrence of norovirus infections among workers exposed to the virus in different outbreak settings.Study designWe screened feces from food handlers and healthcare workers related with gastroenteritis outbreaks, and shedding concentrations over time were calculated from serial samples of infected individuals. Sequence analyses of the capsid P2 domain and region C were used to evaluate linkage between asymptomatic employees and outbreak cases.ResultsOf all employees, 59.1% were positive for NoV, and more than 70% of them were asymptomatic. Asymptomatic infections were significantly more frequent in foodborne compared to person-to-person transmitted outbreaks; and in restaurants and hotels, compared to nursing homes and healthcare institutions. Mean viral loads were similar between symptomatic and asymptomatic individuals, starting at 7.51 ± 1.80 and 6.49 ± 1.93 log₁₀ genome copies/g, respectively, and decreasing to 5.28 ± 0.76 and 4.52 ± 1.45 log₁₀ genome copies/g after 19 days.ConclusionsThe likelihood of becoming infected when a NoV outbreak occurs at the work place is high and similar between food handlers and healthcare workers, but asymptomatic infections are more frequently identified among food handlers. Since shed amounts of viruses in the absence of symptoms are also high, reinforcement of hygiene practices among workers is especially relevant to reduce the risk of virus secondary transmissions.     

Viral excretion and antibody titers in children infected with hepatitis A virus from an orphanage in western India

BackgroundHepatitis A is endemic in India and mainly causes sporadic infections. However, children in childcare centers, schools and orphanages are vulnerable to common-source outbreaks as they have naive hosts.ObjectivesTo investigate hepatitis A outbreak in an orphanage from Pune, India.Study DesignMonitoring of virus excretion and anti-HAV antibody levels in hepatitis A virus (HAV) infected children.ResultsThe orphanage housed 93 children of the age 1 month-6.5 years. Analysis of the collected serum (n = 78) and stool samples (n = 63) revealed 20 children to be either positive for anti-HAV IgM antibodies or excreting HAV, 14 being symptomatic and 6 asymptomatic, while 32 were already anti-HAV IgG positive either due to past HAV exposure (n = 7, mean log antibody titers: 2.96) or maternal antibodies (n = 25, mean log antibody titers: 1.13). Serum samples, taken 4 weeks apart, did not show any significant difference in the IgM and IgG antibody levels either. However, virus excretion decreased significantly after 15 days in symptomatic children (mean log HAV RNA copies/ml 1.03 + 0.30), while asymptomatic children continued to excrete higher viral loads, at constant levels (mean log HAV RNA copies/ml 2.33 + 0.33), for up to 90 days.ConclusionsThough virus excretion continued up to 90 days in all HAV infected children, asymptomatic children excreted higher viral loads for longer period and hence can contribute significantly in person-to-person virus transmission. All children should be vaccinated in such set ups.     

Viral load and genotypes of noroviruses in symptomatic and asymptomatic children in Southeastern Brazil

BackgroundNoroviruses (NoVs) are a major etiological agent of sporadic acute gastroenteritis worldwide.ObjectivesTo detect, quantify and characterize genogroups and genotypes of NoVs in children with and without gastrointestinal symptoms.Study designNoVs were investigated by RT-PCR in a total of 319 fecal specimens from children up to three years old with (n = 229) and without (n = 90) acute diarrhea, between February 2003 and June 2004 in the emergency room in Vitória, Southeastern Brazil. NoVs were quantified by real-time PCR and genotyped.ResultsNoVs were detected in 17% (40/229) and 13% (12/90) of symptomatic and asymptomatic children, respectively. Six NoV-rotavirus A mixed infections were observed. Fifty-one strains were characterized as NoV GII and one as GI. Twenty strains were characterized as GII/4 (9/13), GII/3 (1/13), GII/6 (2/13) and GII/14 (1/13) in symptomatic and GII/3 (6/7) and GII/8 (1/7) in asymptomatic children. The median RNA viral loads were 8.39 and 7.15 log₁₀ copies/g of fecal specimens for symptomatic and asymptomatic children, respectively (p = 0.011). NoV load was lower when it was present in a mixed infection with rotavirus A (p = 0.0005).ConclusionsThis study demonstrates a diversity of NoV strains circulating in this geographic area, and reports GII/8 and GII/14 in the American Continent for the first time. In addition, it confirms GII/4 as the most prevalent genotype in symptomatic children and identified GII/3 in an important frequency, especially in asymptomatic children. Furthermore, preliminary results show that symptomatic patients present a viral load that is significantly greater than asymptomatic children (p = 0.011).     

Emergence of Norovirus GII.4 variants in acute gastroenteritis outbreaks in South Korea between 2006 and 2013

BackgroundNew emerging strains of noroviruses (NoVs) often increase acute gastroenteritis (AGE) outbreaks worldwide.ObjectiveWe analyzed the epidemiological features and genotypic patterns of NoVs in AGE outbreaks.Study designTo elucidate the public health impact of NoVs during AGE outbreaks in South Korea, a molecular and epidemiological investigation was performed with 318 AGE outbreaks reported from the Gyeonggi province of South Korea during the period from 2006 to 2013.ResultsNoVs were associated with 102 (32.1%) of the AGE outbreaks. Epidemiological data revealed that the majority of NoV outbreaks were in the student group (47.1%), and the majority of AGE patients were identified in schools (68.8%). NoV genogroup (G) II strains were associated with 94 (92.2%) of the NoV outbreaks, and GII.4 strains were predominantly associated with 57.6% (n = 49) of NoV GII outbreaks. Four GII.4 variants (2006b, 2007, 2009 and 2012 variants) emerged and showed different contributions to NoV outbreak activity. The 2006b variant was predominantly associated with NoV outbreaks during the early years of the study period, and was subsequently displaced by the New Orleans 2009 variant, and most recently by the Sydney 2012 variant. In addition, the GII.2, GII.14, and GII.17 strains have recently been often associated with NoV AGE outbreaks.ConclusionsThe emergence of new NoV GII.4 variants significantly affected the NoV outbreak activity in South Korea during the period from 2006 to 2013. The surveillance for new emerging strains affecting NoV outbreak activity should be intensified to develop an adequate policy to prevent further NoV outbreaks.     

Norovirus in feces and nasopharyngeal swab of children with and without acute gastroenteritis symptoms: First report of GI.5 in Brazil and GI.3 in nasopharyngeal swab

BackgroundNoroviruses (NoVs) are an important cause of acute gastroenteritis (AGE), worldwide.ObjectivesTo evaluate the frequency, viral load and molecular profile of NoV in fecal and nasopharyngeal swab samples from hospitalized children, and to determine children’s secretor status.Study designFrom May 2014 to May 2015, 219 children were included in the study, 96 with gastroenteric symptoms and 123 without gastroenteric symptoms. All fecal and nasopharyngeal swab samples were screened by TaqMan RT-qPCR duplex (GI/GII NoV) and quality samples were characterized by genomic sequencing.ResultsNorovirus positivity rate in feces was 15.4% in asymptomatic and 18.8% in the symptomatic group. The median viral loads in feces were 2.69 × 10⁸ GC/g and 4.32 × 10⁷ GC/g from children with or without AGE symptoms, respectively. In nasopharyngeal swab samples, the NoV positivity was 11.4% in symptomatic children, with a median viral load of 2.20 × 10⁷ GC/mL and 6.5% in asymptomatic children, with an average viral load of 1.73 × 10⁶ GC/mL. In only two cases NoV was detected in both samples. A considerable genomic variability was observed in feces, with six genotypes being detected, as follows: GII.4, GII.6, GI.3 and GII.3, GI.2 and GI.5. Two GI.3 was detected in nasopharyngeal swab.ConclusionsOur data reveal considerable NoV frequencies in both nasopharyngeal and fecal samples from symptomatic and asymptomatic children. Higher viral loads were detected in samples from AGE symptomatic children, when compared to asymptomatic children. High genomic variability was observed, with this being the first report of GI.5 NoV in Brazil and of GI.3 in nasopharyngeal swab samples.     

Association of plasma viremia with HIV-1 RNA levels in cervicovaginal lavage secretions in HIV-1 seropositive ART naïve women from Pune,India

BackgroundCoherent drug/microbicide/vaccine development research would benefit through a precise knowledge of HIV dissemination and its persistence in the female genital tract. Understanding relationship between plasma viremia and cervicovaginal HIV shedding may help to unveil mechanisms underlying transmission, compartmentalization and pathogenesis.ObjectivesTo study the association between HIV-1 RNA levels in the plasma and CVL specimens.Study designWhole blood, plasma and CVL specimens were collected from 36 ART naïve HIV-1 seropositive women qualifying the study inclusion criteria. Absolute CD4 counts, plasma and CVL HIV-1 RNA levels were estimated using commercially available kits (BD MultiSET™ Kit, Becton Dickinson, US and Abbott RT, Abbott Molecular, Germany). Correlation between plasma and CVL viral load was estimated by the Spearman's rank correlation coefficient. Additionally, the correlation between CVL viral load and absolute CD4 counts was studied.ResultsHIV-1 viral load in the CVL specimens was successfully quantified using the Abbott RT. Twenty-seven of 36 women (75%) had detectable HIV-1 RNA levels in plasma and CVL specimens. The CVL viral load did not show any correlation with plasma viral load (ρ = 0.281, p = 0.096) and showed a ‘moderate correlation’ (ρ = −0.563, p = 0.0004) with absolute CD4 counts.ConclusionsAlbeit, the Abbott RT is designed for estimating plasma HIV-1 RNA levels, the study reports its use for estimating HIV-1 RNA levels in the CVL specimens as well. In accordance with the previous studies, our results suggest that plasma and CVL viral load are not correlated and plasma viremia might not solely predict cervico vaginal HIV shedding.     

Norovirus prevalence and estimated viral load in symptomatic and asymptomatic children from rural communities of Vhembe district,South Africa

BackgroundHuman Norovirus (NoV) is recognized as a major etiological agent of sporadic acute gastroenteritis worldwide.ObjectivesThis study describes the clinical features associated with Human NoV occurrence in children and determines the prevalence and estimated viral burden of NoV in symptomatic and asymptomatic children in rural South Africa.Study designBetween July 2014 and April 2015, outpatient children under 5 years of age from rural communities of Vhembe district, South Africa, were enrolled for the study. A total of 303 stool specimens were collected from those with diarrhea (n = 253) and without (n = 50) diarrhea. NoVs were identified using real-time one-step RT-PCR.ResultsOne hundred and four (41.1%) NoVs were detected (62[59.6%] GII, 16[15.4%] GI, and 26[25%] mixed GI/GII) in cases and 18 (36%) including 9(50%) GII, 2(11.1%) GI and 7(38.9%) mixed GI/GII in controls. NoV detection rates in symptomatic and asymptomatic children (OR = 1.24; 95% CI 0.66⿿2.33) were not significantly different. Comparison of the median C_T values for NoV in symptomatic and asymptomatic children revealed significant statistical difference of estimated GII viral load from both groups, with a much higher viral burden in symptomatic children.ConclusionsThough not proven predictive of diarrhea disease in this study, the high detection rate of NoV reflects the substantial exposure of children from rural communities to enteric pathogens possibly due to poor sanitation and hygiene practices. The results suggest that the difference between asymptomatic and symptomatic children with NoV may be at the level of the viral load of NoV genogroups involved.     

Persistence of varicella-zoster virus viraemia in patients with herpes zoster

BackgroundHerpes zoster is caused by the reactivation of varicella-zoster virus from sensory neurons. The commonest complication following zoster is chronic pain termed post herpetic neuralgia.ObjectivesTo investigate the dynamics of VZV viraemia and viral load following the resolution of zoster and its relationship to PHN development.Study designBlood samples were collected at baseline, 1 month, 3 months and 6 month from a prospective study of 63 patients with active zoster. Quantification of VZV DNA in whole blood was performed using a real-time PCR assay.ResultsDuring acute zoster, all patients had detectable VZV DNA in their blood. VZV DNA remained detectable in the blood of 91% of patients at 6 months although levels declined significantly (p < 0.0001). A history of prodromal symptoms (p = 0.005) and severity of pain at baseline (p = 0.038) as well as taking antivirals (p = 0.046) and being immunocompromised (p = 0.043) were associated, with longer time to recovery from PHN. Viral DNA loads were consistently higher in patients with risk factors for PHN and higher viral DNA loads over time were associated with longer time to recovery (p = 0.058 overall and 0.038 in immunocompetent).ConclusionsBased on these observations we hypothesise that VZV replication persists following acute shingles and that higher viral DNA loads contribute to the risk factors for PHN.     

Effect of artemether-lumefantrine (Coartem) on cytomegalovirus urine viral load during and following treatment for malaria in children

BackgroundArtemisinins, commonly used to treat malaria, have shown activity against cytomegalovirus (CMV) in vitro, in an animal model, and in case reports; however, the in vivo anti-CMV activity has not been well investigated.ObjectivesTo evaluate whether artemisinins affect CMV shedding among subjects co-infected with CMV and malaria.Study designA prospective observational study of children in Mali (6 month–10 year) presenting with fever. Urine samples were collected at day 0, 3, and 14 from children treated with artemether-lumefantrine (Coartem^®) for malaria and those who had other illnesses not treated with Coartem. CMV DNA was quantified using a real-time PCR. Resulting urine viral loads were compared between the groups at three time points.Results164 malaria cases and 143 non-malaria comparisons were enrolled. Eighty-one (49%) cases and 88 (62%) comparisons shed CMV at day 0. Day 0 and day 3 viral loads were similar, but at day 14 the median viral load of cases was lower than that of comparisons (360 vs 720 copies/mL or 2.56 vs 2.86 log₁₀), p = 0.059. A stratified analysis of day 0 high viral shedders (defined as >1000 copies/mL) showed significantly lower median viral load at day 14 among cases (490 copies/mL, 2.69 log₁₀) vs comparisons (1200 copies/mL, 3.08 log₁₀), p = 0.045.ConclusionA high rate of urinary CMV shedding was found in a malaria-endemic area. Among high virus shedders artemether-lumefantrine decreased urine viral load, but the effect was not observed when analysis of both high and low shedders was performed. These results support additional studies of artemisinin dosing and duration in CMV infection.     

Norovirus GII.4 variant 2006b caused epidemics of acute gastroenteritis in Australia during 2007 and 2008

BackgroundOver the last decade, four epidemics of norovirus-associated gastroenteritis have been reported in Australia. These epidemics were characterized by numerous outbreaks in institutional settings such as hospitals and nursing homes, as well as increases in requests for NoV testing in diagnostic centers. During 2007 and 2008, widespread outbreaks of acute gastroenteritis were once again seen across Australia, peaking during the winter months.ObjectivesThe primary objective of this study was to characterize two winter epidemics of NoV-associated gastroenteritis in 2007 and 2008 in Australia. Following this, we aimed to determine if these epidemics were caused by a new GII.4 variant or a previously circulating NoV strain.Study designNoV-positive fecal samples (n = 219) were collected over a 2-year period, December 2006 to December 2008, from cases of acute gastroenteritis in Australia. NoV RNA was amplified from these samples using a nested RT-PCR approach targeting the 5′ end of the capsid gene, termed region C. Further, characterization was performed by sequence analysis of the RdRp and capsid genes and recombination was identified using SimPlot.ResultsFrom 2004 to 2008, peaks in the numbers of NoV-positive EIA tests from the Prince of Wales Hospital Laboratory correlated with the overall number of gastroenteritis outbreaks reported to NSW Health, thereby supporting recent studies showing that NoV is the major cause of outbreak gastroenteritis. The predominant NoV GII variant identified during the 2007–2008 period was the GII.4 pandemic variant, 2006b (71.51%, 128/179), which replaced the 2006a variant identified in the previous Australian epidemic of 2006. Four novel GII variants were also identified including the three GII.4 variants: NoV 2008, NoV Osaka 2007 and NoV Cairo 2007, and one novel recombinant NoV designated GII.e/GII.12.ConclusionThe increase in acute gastroenteritis outbreaks in 2007 and 2008 were associated with the spread of the NoV GII.4 variant 2006b.     

Performance of a rapid antigen test (Binax NOW® RSV) for diagnosis of respiratory syncytial virus compared with real-time polymerase chain reaction in a pediatric population

BackgroundInfants from Alaska's Yukon–Kuskokwim Delta (YKD) have a high respiratory syncytial virus (RSV) hospitalization rate (104/1000/yr). Appropriate patient management requires rapid and accurate RSV diagnosis. Antigen-based methods are often used in clinical settings, but these tests can lack sensitivity.ObjectiveWe compared Binax NOW^® RSV (BN) used for RSV diagnosis in the YKD hospital with a real-time polymerase chain reaction assay (RT-qPCR) used for viral surveillance.Study designBetween October 2005 and September 2007 we obtained nasopharyngeal washes (NPW) from children <3 years hospitalized with a lower respiratory tract infection. The NPW were tested using BN and RT-qPCR.Results79/311 (25%) children had RSV infection as determined by RT-qPCR. As compared with RT-qPCR, sensitivity and specificity of BN were 72% and 97%, respectively. The sensitivity of BN was higher in children <1 year compared with children ≥1 year (79% vs. 52%; p = 0.025), children with bronchiolitis compared with children without bronchiolitis (89% vs. 38%; p < 0.001), and children with a shorter duration of symptoms before testing (0–1 (92%) vs. 2–4 (78%) vs. 5+ (65%) days; p = 0.04). The median RSV viral load in NPW positive by BN and RT-qPCR was 1.01 × 10⁹ copies/mL vs. a median of 5.25 × 10⁷ copies/mL for NPW positive by RT-qPCR only (p < 0.001).ConclusionRT-qPCR is more sensitive than BN in detecting RSV infection. BN sensitivity is high in children with bronchiolitis, but the sensitivity is low when children present with a non-bronchiolitis illness, especially after a longer duration of symptoms before testing.     

Effects of supervised whole body vibration exercise on fall risk factors,functional dependence and health-related quality of life in nursing home residents aged 80+

ObjectiveTo test the feasibility and effectiveness of whole-body vibration (WBV) therapy on fall risk, functional dependence and health-related quality of life in nursing home residents aged 80+ years.DesignTwenty-nine 80–95 years old volunteers, nursing home residents were randomized to an eight-week WBV intervention group) (n = 15) or control group (n = 14). Functional mobility was assessed using the timed up and go (TUG) test. Lower limb performance was evaluated using the 30-s Chair Sit to Stand (30-s CSTS) test. Postural stability was measured using a force platform. The Barthel Index was used to assess functional dependence and the EuroQol (EQ-5D) was used to evaluate Health-Related Quality of Life. All outcome measures were assessed at baseline and at a follow-up after 8 weeks.ResultsAt the 8-week follow up, TUG test (p < 0.001), 30-s CSTS number of times (p = 0.006), EQ-5Dmobility (p < 0.001), EQ-5DVAS (p < 0.014), EQ-5Dutility (p < 0.001) and Barthel index (p = 0.003) improved in the WBV intervention group when compared to the control group.ConclusionsAn 8-week WBV-based intervention in a nursing home setting is effective in reducing fall risk factors and quality of life in nursing home residents aged 80+.     

Epidemiologic,clinical, and virologic characteristics of human rhinovirus infection among otherwise healthy children and adults: Rhinovirus among adults and children

Backgroundhuman rhinovirus (HRV) is a major cause of influenza-like illness (ILI) in adults and children. Differences in disease severity by HRV species have been described among hospitalized patients with underlying illness. Less is known about the clinical and virologic characteristics of HRV infection among otherwise healthy populations, particularly adults.Objectivesto characterize molecular epidemiology of HRV and association between HRV species and clinical presentation and viral shedding.Study designobservational, prospective, facility-based study of ILI was conducted from February 2010 to April 2012. Collection of nasopharyngeal specimens, patient symptoms, and clinical information occurred on days 0, 3, 7, and 28. Patients recorded symptom severity daily for the first 7 days of illness in a symptom diary. HRV was identified by RT-PCR and genotyped for species determination. Cases who were co-infected with other viral respiratory pathogens were excluded from the analysis. We evaluated the associations between HRV species, clinical severity, and patterns of viral shedding.Resultseighty-four HRV cases were identified and their isolates genotyped. Of these, 62 (74%) were >18 years. Fifty-four were HRV-A, 11HRV-B, and 19HRV-C. HRV-C infection was more common among children than adults (59% vs. 10%, P < 0.001). Among adults, HRV-A was associated with higher severity of upper respiratory symptoms compared to HRV-B (P = 0.02), but no such association was found in children. In addition, adults shed HRV-A significantly longer than HRV-C (P trend = 0.01).Conclusionsamong otherwise healthy adults with HRV infection, we observed species-specific differences in respiratory symptom severity and duration of viral shedding.     

Genetic characterisation of Norovirus strains in outpatient children from rural communities of Vhembe district/South Africa, 2014–2015

BackgroundNorovirus (NoV) is now the most common cause of both outbreaks and sporadic non-bacterial gastroenteritis worldwide. However, data supporting the role of NoV in diarrheal disease are limited in the African continent.ObjectivesThis study investigates the distribution of NoV genotypes circulating in outpatient children from rural communities of Vhembe district/South Africa.Study designStool specimens were collected from children under five years of age with diarrhea, and controls without diarrhea, between July 2014 and April 2015. NoV-positive samples, detected previously by Realtime PCR, were analysed using conventional RT-PCR targeting the partial capsid and polymerase genes. Nucleotide sequencing methods were performed to genotype the strains.ResultsThe sequence analyses demonstrated multiple NoV genotypes including GI.4 (13.8%), GI.5 (6.9%), GII.14 (6.9%), GII.4 (31%), GII.6 (3.4%), GII.P15 (3.4%), GII.P21 (3.4%) and GII.Pe (31%). The most prevalent NoV genotypes were GII.4 Sydney 2012 variants (n = 7) among the capsid genotypes, GII.Pe (n = 9) among the polymerase genotypes and GII.Pe/GII.4 Sydney 2012 (n = 8) putative recombinants among the RdRp/Capsid genotypes. Two unassigned GII.4 variants were found.ConclusionsThe findings highlighted NoV genetic diversity and revealed continuous pandemic spread and predominance of GII.Pe/GII.4 Sydney 2012, indicative of increased NoV activity. An unusual RdRp genotype GII.P15 and two unassigned GII.4 variants were also identified from rural settings of the Vhembe district/South Africa. NoV surveillance is warranted to help to inform investigations into NoV evolution and disease burden, and to support on-going vaccine development programmes.     

Association of cytologic grade of anal “Pap” smears with viral loads of human papillomavirus types 16, 18, and 52 detected in the same specimens from men who have sex with men

BackgroundHuman papilloma virus (HPV) load has been linked to cellular abnormalities of the uterine cervix, and proposed as predictors of HPV persistence and progression of dysplasia to cervical cancer. However, the association of HPV viral load and anal dysplasia and cancer has not been as thoroughly investigated.ObjectivesTo examine the association of the viral loads of high-risk HPV types 16, 18, and 52, with the cytologic severity grading in anal-swab specimens of MSM with and without HIV-1 co-infection.Study designA cross-sectional study recruited 200 MSM in northern Thailand from July 2012 to January 2013. Real-time qPCR amplified portion of the HPV E6E7 gene, as well as the human β-globin gene to validate adequacy of the anal specimens and to normalize interpatient viral-load comparisons. Genotyping by linear-array assay identified and distinguished types 16, 18, and 52.ResultsHPV-16, and -18 viral loads increased with respect to the abnormality of the cytologic diagnoses (p < 0.05 for HPV-16, p < 0.01 for HPV-18). HIV-1 positivity was associated with higher HPV-18 viral load (p = 0.006). HPV-16 viral loads ≥10^2.24 copies per 5000 anal cells, and HPV-18 loads ≥10^3.15, were independently associated with abnormal cytology on logistic regression (p = 0.022, p = 0.041, respectively). Positive predictive values were 85.2% (23/27) and 80.0% (44/55) for the high viral load of a particular HPV-16 and the combined HPV-16, -18 and -52 types, respectively.ConclusionsHigh viral loads of HPV types 16 and 18 appear to be associated with anal cytologic abnormalities. The clinical utility of HPV viral loads to predict risk for anal cancer remains to be determined by a larger prospective cohort with sufficient frequency of high-grade dysplasia.     

Rhino/enteroviruses in hospitalized children: A comparison to influenza viruses

BackgroundThe relative impact of human rhino/enteroviruses (HRV/EV) compared to influenza viruses on hospitalized children is unknown.ObjectivesThis retrospective study compared the epidemiology and clinical characteristics of hospitalized patients with HRV/EV to patients hospitalized with influenza virus.Study designRespiratory specimens from hospitalized children submitted between January 1, 2009 and December 31, 2009 to Children's Hospital Colorado Virology Laboratory in Aurora, CO were tested by a commercial multiplex PCR for 16 respiratory viruses and subtypes. Patients with specimens positive for HRV/EV or influenza virus without bacterial or viral co-infection were selected for retrospective chart review.ResultsOf the 2299 patients with specimens tested during the study period, 427 (18.6%) were singly positive for HRV/EV and 202 (8.8%) for influenza virus (p < 0.01). Children with HRV/EV were more likely to present with increased work of breathing (67.9% vs. 52.5%, p < 0.01) with crackles (36.3% vs. 23.3%, p < 0.01) and wheezing (41.7% vs. 22.8%, p < 0.01) noted on exam. Children hospitalized with HRV/EV had a shorter median length of stay (2 days vs. 3 days, p < 0.01), duration of fever (1 days vs. 3 days, p < 0.01), and duration of hypoxemia (2 days vs. 3 days, p < 0.01) than children with influenza virus. Similar percentages of children with HRV/EV and influenza virus were admitted to the PICU and required positive pressure ventilation. There were no deaths in children hospitalized with HRV/EV, whereas 6 children with influenza virus expired.ConclusionsHRV/EVs are common pathogens in hospitalized children associated with serious lower respiratory tract disease and significant morbidity, similar to influenza viruses.     

Influenza and rhinovirus viral load and disease severity in upper respiratory tract infections

BackgroundThe role of viral load in respiratory viral infection is unclear. It is proposed that the viral load of some, but not all respiratory viruses correlate with disease severity.ObjectivesWe aimed to determine if an association exists between viral loads among patients in ambulatory settings, compared to those requiring hospitalization/intensive care unit (ICU) admission with influenza A/H3N2, influenza B, or human rhinovirus (HRV); we also explored the impact of age, gender and co-detection of Streptococcus pneumoniae on patient setting. We hypothesized that hospitalized/ICU patients have higher respiratory virus viral loads compared to ambulatory (e.g. walk-in clinics, family practices)/ER patients.Study designWe quantified viral load by in-house real-time RT-PCR in 774 nasopharyngeal swabs with influenza A/H3N2, or B or HRV viruses from various patient settings in Ontario, Canada.ResultsMean viral load (log₁₀ copies/ml) of influenza A/H3N2 (6.94) was higher than influenza B (4.96) and HRV (5.58) (p < 0.0001). Influenza A/H3N2 viral loads were highest in infants and the elderly; however, increased A/H3N2 viral loads were not associated with hospitalization/ICU admission compared to swabs collected in ambulatory/ER settings. Influenza B viral loads were higher in patients in hospital/ICU settings compared to those in ambulatory settings (OR 1.28, 95% CI 1.11–1.47). HRV viral loads did not differ by age (p = 0.67) or setting (p = 0.54); there was no association between S. pneumoniae colonization and setting for any virus.ConclusionWhen compared to ambulatory/ER patients, viral load was higher in hospitalized/ICU patients with influenza B, but not influenza A or HRV.     

Serologic evidence for hepatitis E virus infection among patients with undifferentiated acute febrile illness in Kibera,Kenya

BackgroundHepatitis E (HEV) is an emerging cause of viral hepatitis mainly transmitted through the fecal-oral route. Residents of the Kibera slum of Nairobi, Kenya are at risk for fecal-orally transmitted infections.ObjectiveTo quantify the incidence and prevalence of HEV infection among acute febrile illness (AFI) cases using a population-based infectious disease surveillance network.Study designCross-sectional serum samples from AFI case-patients between 2009 and 2012 were matched to the age and gender distribution of the Kibera population and tested by IgM and IgG enzyme immunoassays (EIA) and nucleic acid testing (NAT). Serum from healthy residents was also tested by EIA.ResultsOf the 482 AFI serum samples tested, 124 (25.7%) and 182 (37.8%) were IgM and IgG reactive, respectively. On multivariate analysis, IgM reactivity was associated with HIV (RR 1.66, 95%CI 1.07, 2.60; p = 0.024) while IgG reactivity was associated with increasing age (p < 0.001) and HIV (RR 1.93, 95%CI 1.52, 2.46; p < 0.001). AFI case-patients were more likely to be IgM (p = 0.002) and IgG (p<0.001) reactive compared to healthy residents. The seroincidence by HEV-specific IgM was 84.0 per 1000 person years, however, all 482 samples were negative by NAT.ConclusionsSerologic evidence for HEV in Kibera suggests a high burden of infection, but NAT did not confirm HEV viremia. Additional testing is needed to determine whether EIAs are susceptible to false positivity in undifferentiated AFI populations before their widespread use.     

Microbial translocation is associated with residual viral replication in HAART-treated HIV+ subjects with <50 copies/ml HIV-1 RNA

BackgroundRecent data have shown that plasma levels of lipopolysaccharide (LPS) are a quantitative indicator of microbial translocation in HIV infected individuals.ObjectivesTo assess the impact of residual viral replication on plasma LPS in HAART-treated HIV+ subjects with <50 copies/ml HIV-1 RNA and to evaluate LPS changes during repeated HAART interruptions not exceeding 2-month duration.Study designLPS was measured in 44 HIV+ subjects at T0 (during HAART) and at day 15 of the first and fourth HAART interruption. Ten uninfected, healthy donors were studied as well. Residual plasma HIV-1 RNA was measured at T0 by an ultra-ultrasensitive method with limit of detection of 2.5 copies HIV-1 RNA/ml. Subjects with less than 2.5 copies/ml (fully suppressed – FS) were compared to those with 2.5–50 copies/ml (partially suppressed – PS).ResultsAt T0, plasma LPS levels were comparable in FS and uninfected subjects, whereas in PS they were higher than in uninfected subjects (p = 0.049). After 4 HAART interruptions, they did not change significantly. However, LPS values were lower in FS than in PS (p = 0.020). An inverse correlation was found between CD4 and LPS levels (p = 0.044) in PS group only.ConclusionsA reduced degree of microbial translocation was seen in subjects with a more complete suppression of viral replication. Repeated HAART interruptions had no significant impact on plasma LPS levels.