Orienka Hellferscee

High Nasopharyngeal Pneumococcal Density, Increased by Viral Coinfection, Is Associated With Invasive Pneumococcal Pneumonia

BACKGROUND We identified factors associated with pneumococcal colonization, high colonization density, and invasive pneumococcal pneumonia among patients hospitalized with acute lower respiratory tract infections (ALRTIs). METHODS In 2010, 4025 cases were enrolled in surveillance in South Africa. A total of 969 of 4025 systematically selected nasopharyngeal-oropharyngeal specimens (24%) were tested for respiratory viruses and Streptococcus pneumoniae by real-time polymerase chain reaction. Of these, 749 (77%) had blood tested for S. pneumoniae. RESULTS Pneumococcal colonization was detected in 55% of cases (534 of 969). On multivariable analysis that controlled for age and tuberculosis treatment, infection with influenza virus (adjusted odds ratio [OR], 2.2; 95% confidence interval [CI], 1.1-4.5), adenovirus (adjusted OR, 1.7; 95% CI, 1.1-2.7), rhinovirus (adjusted OR, 1.6; 95% CI, 1.1-2.3), and human immunodeficiency virus (HIV; adjusted OR, 1.6; 95% CI, 1.1-2.4) were associated with pneumococcal colonization. High colonization density was associated with respiratory virus coinfection (adjusted OR, 1.7; 95% CI, 1.1-2.6) and invasive pneumococcal pneumonia (adjusted OR, 2.3; 95% CI, 1.3-4.0), after adjustment for age and sex. Seven percent (52 of 749) had pneumococci detected in blood. On multivariable analysis among colonized cases, invasive pneumococcal pneumonia was associated with HIV (adjusted OR, 3.2; 95% CI, 1.4-7.5), influenza virus (adjusted OR, 8.2; 95% CI, 2.7-25.0), high colonization density (adjusted OR, 18.7; 95% CI, 2.3-155.1), and ≥5 days of hospitalization (adjusted OR, 3.7; 95% CI, 1.7-8.2). CONCLUSIONS Respiratory virus infection was associated with elevated colonization density and, in turn, invasive pneumococcal pneumonia.

Epidemiology of Viral-associated Acute Lower Respiratory Tract Infection Among Children <5 Years of Age in a High HIV Prevalence Setting, South Africa, 2009–2012

Background: Data on the epidemiology of viral-associated acute lower respiratory tract infection (LRTI) from high HIV prevalence settings are limited. We aimed to describe LRTI hospitalizations among South African children aged <5 years. Methods: We prospectively enrolled hospitalized children with physician-diagnosed LRTI from 5 sites in 4 provinces from 2009 to 2012. Using polymerase chain reaction (PCR), nasopharyngeal aspirates were tested for 10 viruses and blood for pneumococcal DNA. Incidence was estimated at 1 site with available population denominators. Results: We enrolled 8723 children aged <5 years with LRTI, including 64% <12 months. The case-fatality ratio was 2% (150/8512). HIV prevalence among tested children was 12% (705/5964). The overall prevalence of respiratory viruses identified was 78% (6517/8393), including 37% rhinovirus, 26% respiratory syncytial virus (RSV), 7% influenza and 5% human metapneumovirus. Four percent (253/6612) tested positive for pneumococcus. The annual incidence of LRTI hospitalization ranged from 2530 to 3173/100,000 population and was highest in infants (8446–10532/100,000). LRTI incidence was 1.1 to 3.0-fold greater in HIV-infected than HIV-uninfected children. In multivariable analysis, compared to HIV-uninfected children, HIV-infected children were more likely to require supplemental-oxygen [odds ratio (OR): 1.3, 95% confidence interval (CI): 1.1–1.7)], be hospitalized >7 days (OR: 3.8, 95% CI: 2.8–5.0) and had a higher case-fatality ratio (OR: 4.2, 95% CI: 2.6–6.8). In multivariable analysis, HIV-infection (OR: 3.7, 95% CI: 2.2–6.1), pneumococcal coinfection (OR: 2.4, 95% CI: 1.1–5.6), mechanical ventilation (OR: 6.9, 95% CI: 2.7–17.6) and receipt of supplemental-oxygen (OR: 27.3, 95% CI: 13.2–55.9) were associated with death. Conclusions: HIV-infection was associated with an increased risk of LRTI hospitalization and death. A viral pathogen, commonly RSV, was identified in a high proportion of LRTI cases.

Epidemiology of severe acute respiratory illness (SARI) among adults and children aged ≥5 years in a high HIV-prevalence setting, 2009-2012.

Objective There are few published studies describing severe acute respiratory illness (SARI) epidemiology amongst older children and adults from high HIV-prevalence settings. We aimed to describe SARI epidemiology amongst individuals aged ≥5 years in South Africa. Methods We conducted prospective surveillance for individuals with SARI from 2009–2012. Using polymerase chain reaction, respiratory samples were tested for ten viruses, and blood for pneumococcal DNA. Cumulative annual SARI incidence was estimated at one site with population denominators. Findings We enrolled 7193 individuals, 9% (621/7067) tested positive for influenza and 9% (600/6519) for pneumococcus. HIV-prevalence was 74% (4663/6334). Among HIV-infected individuals with available data, 41% of 2629 were receiving antiretroviral therapy (ART). The annual SARI hospitalisation incidence ranged from 325-617/100,000 population. HIV-infected individuals experienced a 13–19 times greater SARI incidence than HIV-uninfected individuals (p<0.001). On multivariable analysis, compared to HIV-uninfected individuals, HIV-infected individuals were more likely to be receiving tuberculosis treatment (odds ratio (OR):1.7; 95%CI:1.1–2.7), have pneumococcal infection (OR 2.4; 95%CI:1.7–3.3) be hospitalised for >7 days rather than <2 days (OR1.7; 95%CI:1.2–2.2) and had a higher case-fatality ratio (8% vs 5%;OR1.7; 95%CI:1.2–2.3), but were less likely to be infected with influenza (OR 0.6; 95%CI:0.5–0.8). On multivariable analysis, independent risk indicators associated with death included HIV infection (OR 1.8;95%CI:1.3–2.4), increasing age-group, receiving mechanical ventilation (OR 6.5; 95%CI:1.3–32.0) and supplemental-oxygen therapy (OR 2.6; 95%CI:2.1–3.2). Conclusion The burden of hospitalized SARI amongst individuals aged ≥5 years is high in South Africa. HIV-infected individuals are the most important risk group for SARI hospitalization and mortality in this setting.

Epidemiology of Influenza Virus Types and Subtypes in South Africa, 2009–2012

Patient age and co-infections, but not disease severity, were associated with virus type and subtype.

The role of influenza, RSV and other common respiratory viruses in severe acute respiratory infections and influenza-like illness in a population with a high HIV sero-prevalence, South Africa, 2012-2015

BACKGROUND Viruses detected in patients with acute respiratory infections may be the cause of illness or asymptomatic shedding. OBJECTIVE To estimate the attributable fraction (AF) and the detection rate attributable to illness for each of the different respiratory viruses STUDY DESIGN We compared the prevalence of 10 common respiratory viruses (influenza A and B viruses, parainfluenza virus 1-3; respiratory syncytial virus (RSV); adenovirus, rhinovirus, human metapneumovirus (hMPV) and enterovirus) in both HIV positive and negative patients hospitalized with severe acute respiratory illness (SARI), outpatients with influenza-like illness (ILI), and control subjects who did not report any febrile, respiratory or gastrointestinal illness during 2012-2015 in South Africa. RESULTS We enrolled 1959 SARI, 3784 ILI and 1793 controls with a HIV sero-prevalence of 26%, 30% and 43%, respectively. Influenza virus (AF: 86.3%; 95%CI: 77.7-91.6%), hMPV (AF: 85.6%; 95%CI: 72.0-92.6%), and RSV (AF: 83.7%; 95%CI: 77.5-88.2%) infections were associated with severe disease., while rhinovirus (AF: 46.9%; 95%CI: 37.6-56.5%) and adenovirus (AF: 36.4%; 95%CI: 20.6-49.0%) were only moderately associated. CONCLUSIONS Influenza, RSV and hMPV can be considered pathogens if detected in ILI and SARI while rhinovirus and adenovirus were commonly identified in controls suggesting that they may cause only a proportion of clinical disease observed in positive patients. Nonetheless, they may be important contributors to disease.

Genetic diversity and molecular epidemiology of human rhinoviruses in South Africa

Rhinoviruses (RV) are a well‐established cause of respiratory illness. RV‐C has been associated with more severe illness. We aimed to characterize and compare the clinical presentations and disease severity of different RV type circulating in South Africa.

Risk Factors for Influenza-Associated Severe Acute Respiratory Illness Hospitalization in South Africa, 2012–2015

Abstract Background Data on risk factors for influenza-associated hospitalizations in low- and middle-income countries are limited. Methods We conducted active syndromic surveillance for hospitalized severe acute respiratory illness (SARI) and outpatient influenza-like illness (ILI) in 2 provinces of South Africa during 2012–2015. We compared the characteristics of influenza-positive patients with SARI to those with ILI to identify factors associated with severe disease requiring hospitalization, using unconditional logistic regression. Results During the study period, influenza virus was detected in 5.9% (110 of 1861) and 15.8% (577 of 3652) of SARI and ILI cases, respectively. On multivariable analysis factors significantly associated with increased risk of influenza-associated SARI hospitalization were as follows: younger and older age (<6 months [adjusted odds ratio {aOR}, 37.6], 6–11 months [aOR, 31.9], 12–23 months [aOR, 22.1], 24–59 months [aOR, 7.1], and ≥65 years [aOR, 40.7] compared with 5–24 years of age), underlying medical conditions (aOR, 4.5), human immunodeficiency virus infection (aOR, 4.3), and Streptococcus pneumoniae colonization density ≥1000 deoxyribonucleic acid copies/mL (aOR, 4.8). Underlying medical conditions in children aged <5 years included asthma (aOR, 22.7), malnutrition (aOR, 2.4), and prematurity (aOR, 4.8); in persons aged ≥5 years, conditions included asthma (aOR, 3.6), diabetes (aOR, 7.1), chronic lung diseases (aOR, 10.7), chronic heart diseases (aOR, 9.6), and obesity (aOR, 21.3). Mine workers (aOR, 13.8) and pregnant women (aOR, 12.5) were also at increased risk for influenza-associated hospitalization. Conclusions The risk groups identified in this study may benefit most from annual influenza immunization, and children <6 months of age may be protected through vaccination of their mothers during pregnancy.

Human metapneumovirus-associated severe acute respiratory illness hospitalisation in HIV-infected and HIV-uninfected South African children and adults

BACKGROUND Data on human metapneumovirus (HMPV)-associated severe acute respiratory illness (SARI) are limited in settings with high human immunodeficiency virus (HIV) infection prevalence. OBJECTIVES To describe clinical characteristics and seasonality (all sites), and incidence (Soweto only) of HMPV-associated SARI among children and adults. STUDY DESIGN Active, prospective, hospital-based, sentinel surveillance for patients hospitalised with SARI was conducted at four sites in South Africa from February 2009-December 2013. Upper respiratory tract samples were tested by multiplex real-time polymerase chain reaction assays for HMPV and other respiratory viruses. Incidence of hospitalisation, stratified by age and HIV-infection status, was calculated for one hospital with population denominators. RESULTS HMPV was identified in 4.1% of patients enrolled, including 5.6% (593/10503) in children and 1.7% in adults (≥18 years; 119/6934). The majority of adults (84.0%) had an underlying medical condition, including HIV infection in 87/110 (79.1%). HMPV detection occurred perennially with periods of increased detection, which varied from year to year. The incidence of HMPV-associated hospitalisation in Soweto was highest in infants (653.3 per 100,000 person years; 95% confidence interval (CI) 602.2-707.6). The incidence was higher in HIV-infected persons compared to HIV-uninfected persons in age-groups 5-17 years (RR 6.0; 1.1-20.4), 18-44 years (RR 67.6; 38.0-132.6) and 45-64 years (RR 5.3; 3.4-8.3), while not differing in other age-groups. CONCLUSIONS The burden of HMPV-associated SARI hospitalisation among adults occurred predominantly in HIV-infected persons. Among children, infants were at highest risk, with similar burden of hospitalisation in HIV-infected and HIV-uninfected children.

Epidemiology of influenza B/Yamagata and B/Victoria lineages in South Africa, 2005-2014

Background Studies describing the epidemiology of influenza B lineages in South Africa are lacking. Methods We conducted a prospective study to describe the circulation of influenza B/Victoria and B/Yamagata lineages among patients of all ages enrolled in South Africa through three respiratory illness surveillance systems between 2005 and 2014: (i) the Viral Watch (VW) program enrolled outpatients with influenza-like illness (ILI) from private healthcare facilities during 2005–2014; (ii) the influenza-like illnesses program enrolled outpatients in public healthcare clinics (ILI/PHC) during 2012–2014; and (iii) the severe acute respiratory illnesses (SARI) program enrolled inpatients from public hospitals during 2009–2014. Influenza B viruses were detected by virus isolation during 2005 to 2009 and by real-time reverse transcription polymerase chain reaction from 2009–2014. Clinical and epidemiological characteristics of patients hospitalized with SARI and infected with different influenza B lineages were also compared using unconditional logistic regression. Results Influenza viruses were detected in 22% (8,706/39,804) of specimens from patients with ILI or SARI during 2005–2014, of which 24% (2,087) were positive for influenza B. Influenza B viruses predominated in all three surveillance systems in 2010. B/Victoria predominated prior to 2011 (except 2008) whereas B/Yamagata predominated thereafter (except 2012). B lineages co-circulated in all seasons, except in 2013 and 2014 for SARI and ILI/PHC surveillance. Among influenza B-positive SARI cases, the detection of influenza B/Yamagata compared to influenza B/Victoria was significantly higher in individuals aged 45–64 years (adjusted odds ratio [aOR]: 4.2; 95% confidence interval [CI]: 1.1–16.5) and ≥65 years (aOR: 12.2; 95% CI: 2.3–64.4) compared to children aged 0–4 years, but was significantly lower in HIV-infected patients (aOR: 0.4; 95% CI: 0.2–0.9). Conclusion B lineages co-circulated in most seasons except in 2013 and 2014. Hospitalized SARI cases display differential susceptibility for the two influenza B lineages, with B/Victoria being more prevalent among children and HIV-infected persons.

Severity of respiratory syncytial virus lower respiratory tract infection with viral coinfection in HIV-uninfected children

Summary: It is not clear why some children have life-threatening RSV disease. We found RSV and any viral coinfection compared to RSV monoinfection is not associated with more severe disease. Increased life-threatening disease in RSV-ADV and RSV-Influenza coinfection warrants further study.