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11.
  • Groome, Michelle J., et al. (author)
  • Human metapneumovirus-associated severe acute respiratory illness hospitalisation in HIV-infected and HIV-uninfected South African children and adults
  • 2015
  • In: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532 .- 1873-5967. ; 69, s. 125-132
  • Journal article (peer-reviewed)abstract
    • 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.
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12.
  • Madhi, Shabir A., et al. (author)
  • Residual colonization by vaccine serotypes in rural South Africa four years following initiation of pneumococcal conjugate vaccine immunization
  • 2020
  • In: Expert Review of Vaccines. - : Taylor & Francis. - 1476-0584 .- 1744-8395. ; 19:4, s. 383-393
  • Journal article (peer-reviewed)abstract
    • Background: We evaluated pneumococcal colonization in children and adults between the time of 7-valent pneumococcal conjugate vaccine (PCV) introduction in the immunization program in 2009 to two years after transitioning to PCV13 in 2011.Methods: Community-based carriage surveillance was undertaken between May-November 2013 (Period-3), with similar surveys in 2009 (Period-1) and 2011 (Period-2). Households with children below two years had a similar probability of being sampled in all surveys. Nasopharyngeal swabs were processed using standard methods and serotyped by Quellung.Results: In children>9-59 months old, overall pneumococcal colonization prevalence declined from 81.8% in Period-1 to 65.0% in Period-3 (p<0.001). Reductions of 70% (41.2% vs. 13.6%) in PCV7-serotypes colonization and 66% (15.3% vs. 4.4%) for the six additional PCV13-serotypes (PCV13-add6VT) were observed. There was, however, high residual colonization by PCV7-serotypes 19F (14.9% vs. 6.3%) and 23F (8.5% vs. 4.1%), despite reduction of 57% and 52%, respectively. Among individuals>12 years of age, there was 61% reduction in PCV7-serotype colonization (3.1% vs. 1.3%) and 75% decrease for PCV13-add6VT (2.1% vs. 0.6%) between Period-1 and Period-3.Conclusions: The residual prevalence of serotypes 19F and 23F, four years after introducing PCV in the South Africa, suggests ongoing community transmission and transient vaccine effects.
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13.
  • Moyes, Jocelyn, et al. (author)
  • Epidemiology of Respiratory Syncytial Virus-Associated Acute Lower Respiratory Tract Infection Hospitalizations Among HIV-Infected and HIV-Uninfected South African Children, 2010-2011
  • 2013
  • In: Journal of Infectious Diseases. - : Oxford University Press. - 0022-1899 .- 1537-6613. ; 208:Supplement: 3, s. S217-S226
  • Journal article (peer-reviewed)abstract
    • Background. There are limited data on respiratory syncytial virus (RSV) infection among children in settings with a high prevalence of human immunodeficiency virus (HIV). We studied the epidemiology of RSV-associated acute lower respiratory tract infection (ALRTI) hospitalizations among HIV-infected and HIV-uninfected children in South Africa. Methods. Children aged <5 years admitted to sentinel surveillance hospitals with physician-diagnosed neonatal sepsis or ALRTI were enrolled. Nasopharyngeal aspirates were tested by multiplex real-time polymerase chain reaction assays for RSV and other viruses. Associations between possible risk factors and severe outcomes for RSV infection among HIV-infected and uninfected children were examined. The relative risk of hospitalization in HIV-infected and HIV-uninfected children was calculated in 1 site with population denominators. Results. Of 4489 participants, 4293 (96%) were tested for RSV, of whom 1157 (27%) tested positive. With adjustment for age, HIV-infected children had a 3-5-fold increased risk of hospitalization with RSV-associated ALRTI (2010 relative risk, 5.6; [95% confidence interval (CI), 4.5-6.4]; 2011 relative risk, 3.1 [ 95% CI, 2.6-3.6]). On multivariable analysis, HIV-infected children with RSV-associated ALRTI had higher odds of death (adjusted odds ratio. 31.1; 95% CI, 5.4-179.8) and hospitalization for >5 days (adjusted odds ratio, 4.0; 95% CI, 1.5-10.6) than HIV-uninfected children. Conclusion. HIV-infected children have a higher risk of hospitalization with RSV-associated ALRTI and a poorer outcome than HIV-uninfected children. These children should be targeted for interventions aimed at preventing severe RSV disease.
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14.
  • Moyes, Jocelyn, et al. (author)
  • Respiratory syncytial virus in adults with severe acute respiratory illness in a high HIV prevalence setting
  • 2017
  • In: Journal of Infection. - : Saunders Elsevier. - 0163-4453 .- 1532-2742. ; 75:4, s. 346-355
  • Journal article (peer-reviewed)abstract
    • Background: There are limited data on the epidemiology of respiratory syncytial virus (RSV) illness in HIV-infected adults or the elderly in Africa. We studied the epidemiology of RSV-associated severe acute respiratory illness (SARI) hospitalizations in adults in South Africa from 2009 through 2013. Methods: Individuals admitted to sentinel surveillance hospitals were investigated by respiratory tract swabs for RSV, using a multiplex real-time polymerase chain reaction assay. The incidence of RSV-associated SARI was calculated for the one site with population denominators. Results: Of 7796 participants investigated, 329 (4%) tested positive for RSV. On multivariable analysis, HIV-infected individuals with RSV-associated SARI had greater odds of being in the age groups 18-44 and 45-64 years (odd ratios (OR) 26.3; 95% confidence interval (CI) 6.2-112.1 and OR 11.4; 95% CI 2.6-50.0) compared with those >= 65 years and being female (OR 2.7; 95% CI 1.4-5.4). The relative risk of hospitalization with RSV-associated SARI was 12-18 times higher in HIV infected individual compared to that of HIV-uninfected. Conclusion: The incidence of RSV-associated SARI was higher in HIV-infected individuals and those aged 65 years and older. Further studies are warranted to describe the disease association of RSV detected in adults with SARI.
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15.
  • Msimang, Veerle M. Y., et al. (author)
  • Impact of Rotavirus Vaccine on Childhood Diarrheal Hospitalization After Introduction Into the South African Public Immunization Program
  • 2013
  • In: The Pediatric Infectious Disease Journal. - : Lippincott Williams & Wilkins. - 0891-3668 .- 1532-0987. ; 32:12, s. 1359-1364
  • Journal article (peer-reviewed)abstract
    • Background: Oral rotavirus vaccine was introduced into the South African routine immunization program in August 2009 administered at 6 and 14 weeks with no catch-up. We described the change in rotavirus-associated diarrheal hospitalizations among children <5 years at 3 sentinel sites from 2009 through 2011. Methods: During 2009 through 2011, we compared the proportion of enrolled children aged <5 years hospitalized with acute gastroenteritis and testing rotavirus positive. We used hospital data to determine the change in diarrhea hospitalizations and estimated total numbers of rotavirus hospitalizations by adjusting for nonenrolled patients. Stool samples were tested for rotavirus using enzyme immunoassay. Results: In 2009 (May-December), 46% (404/883) of samples among children <5 years tested rotavirus positive, decreasing to 33% (192/580) (P < 0.001) in 2010 and 29% (113/396) (P < 0.001) in 2011. Compared with May-December 2009, total diarrhea hospitalizations among children aged <5 years was one-third lower in May-December of 2010 and 2011. Among infants, adjusted rotavirus hospitalizations were 61% (n = 267) and 69% (n = 214) lower, respectively, in 2010 and 2011 when compared with 2009 (n = 689), and 45 and 50 percentage points greater than the reduction in rotavirus-negative cases. Among children <5 years, rotavirus hospitalizations were 54% and 58% lower in 2010 and 2011, compared with 2009 (40 and 44 percentage points greater than reduction in rotavirus-negative cases). Rotavirus reductions occurred in rural and urban settings. Conclusion: Using published estimates of rotavirus hospitalization burden, we estimate that at least 13,000 to 20,000 hospitalizations in children <2 years were prevented in the 2 years after rotavirus vaccine introduction.
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16.
  • Murray, Jillian, et al. (author)
  • Determining the Provincial and National Burden of Influenza-Associated Severe Acute Respiratory Illness in South Africa Using a Rapid Assessment Methodology
  • 2015
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:7
  • Journal article (peer-reviewed)abstract
    • Local disease burden data are necessary to set national influenza vaccination policy. In 2010 the population of South Africa was 50 million and the HIV prevalence was 11%. We used a previously developed methodology to determine severe influenza burden in South Africa. Hospitalized severe acute respiratory illness (SARI) incidence was calculated, stratified by HIV status, for four age groups using data from population-based surveillance in one site situated in Gauteng Province for 2009-2011. These rates were adjusted for each of the remaining 8 provinces based on their prevalence of risk factors for pneumonia and healthcare-seeking behavior. We estimated non-hospitalized influenza-associated SARI from healthcare utilization surveys at two sites and used the percent of SARI cases positive for influenza from sentinel surveillance to derive the influenza-associated SARI rate. We applied rates of hospitalized and non-hospitalized influenza-associated SARI to census data to calculate the national number of cases. The percent of SARI cases that tested positive for influenza ranged from 7-17% depending on age group, year, province and HIV status. In 2010, there were an estimated 21,555 total severe influenza cases in HIV-uninfected individuals and 13,876 in HIV-infected individuals. In 2011, there were an estimated 29,892 total severe influenza cases in HIV-uninfected individuals and 17,289 in HIV-infected individuals. The incidence of influenza-associated SARI was highest in children <5 years and was higher in HIV-infected than HIV-uninfected persons in all age groups. Influenza virus was associated with a substantial amount of severe disease, especially in young children and HIV-infected populations in South Africa.
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17.
  • Nzenze, Susan A, et al. (author)
  • Temporal changes in pneumococcal colonization in a rural African community with high HIV prevalence following routine infant pneumococcal immunization
  • 2013
  • In: The Pediatric Infectious Disease Journal. - : Ovid Technologies (Wolters Kluwer Health). - 0891-3668 .- 1532-0987. ; 32:11, s. 1270-1278
  • Journal article (peer-reviewed)abstract
    • Background: Pneumococcal conjugate vaccine (PCV) immunization of children decreases their risk of nasopharyngeal acquisition of vaccine serotypes. We studied the impact of routine infant PCV immunization alone on the epidemiology of nasopharyngeal pneumococcal colonization among a rural African community with high prevalence of HIV positivity.Methods: Two cross-sectional surveys were undertaken in a rural South African community from May to October 2009 (period 1) and 2011 (period 2). Seven-valent PCV was introduced into the public immunization program for infants in April 2009, without catch-up campaign for older children. Randomly selected households with at least 1 child <2 years of age were recruited. Nasopharyngeal swabs from all consenting household members were obtained for Streptococcus pneumoniae culture and serotyping by Quellung method.Results: The median ages (SD) of children enrolled were 4.32 (SD, 3.4) and 3.80 (SD, 3.4) years in periods 1 and 2, respectively. Overall, the prevalence of vaccine serotype colonization declined from 18.3% (368/2010) in period 1 to 11.4% (418/3659) by period 2 (P < 0.0001). This included reductions (adjusted risk ratio) of 50% [95% confidence interval (95% CI): 0.42-0.59], 34% (95% CI: 0.48-0.92) and 64% (95% CI: 0.18-0.74) in age groups < 2 years, 6-12 years and adults. The prevalence of vaccine serotype colonization among primary caregivers decreased from 10.2% to 5.4% (P <= 0.001) by period 2. The prevalence of nonvaccine serotype colonization increased by 35% (95% CI: 1.17-1.56) among <2-year-old children by period 2, while it declined by 45-54% among adolescents and adults.Conclusions: An indirect effect of PCV7 was realized in a high HIV prevalence setting within 2 years of PCV introduction. The unexpected decline in nonvaccine serotypes colonization among adolescents/adults may indicate lag in replacement colonization by nonvaccine serotypes in this group.
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18.
  • Rha, Brian, et al. (author)
  • Performance of Surveillance Case Definitions in Detecting Respiratory Syncytial Virus Infection Among Young Children Hospitalized With Severe Respiratory Illness : South Africa, 2009-2014
  • 2019
  • In: Journal of the Pediatric Infectious Diseases Society. - : Oxford University Press. - 2048-7193 .- 2048-7207. ; 8:4, s. 325-333
  • Journal article (peer-reviewed)abstract
    • Background: Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection (ALRTI) in young children, but data on surveillance case definition performance in estimating burdens have been limited.Methods: We enrolled children aged <5 years hospitalized for ALRTI (or neonatal sepsis in young infants) through active prospective surveillance at 5 sentinel hospitals in South Africa and collected nasopharyngeal aspirates from them for RSV molecular diagnostic testing between 2009 and 2014. Clinical data were used to characterize RSV disease and retrospectively evaluate the performance of respiratory illness case definitions (including the World Health Organization definition for severe acute respiratory infection [SARI]) in identifying hospitalized children with laboratory-confirmed RSV according to age group (<3, 3-5, 6-11, 12-23, and 24-59 months).Results: Of 9969 hospitalized children, 2723 (27%) tested positive for RSV. Signs and symptoms in RSV-positive children varied according to age; fever was less likely to occur in children aged <3 months (57%; odds ratio [OR], 0.8 [95% CI, 0.7-0.9]) but more likely in those aged >= 12 months (82%; OR, 1.7-1.9) than RSV-negative children. The sensitivity (range, 55%-81%) and specificity (range, 27%-54%) of the SARI case definition to identify hospitalized RSV-positive children varied according to age; the lowest sensitivity was for infants aged <6 months. Using SARI as the case definition would have missed 36% of RSV-positive children aged <5 years and 49% of those aged <3 months; removing the fever requirement from the definition recovered most missed cases.Conclusion: Including fever in the SARI case definition lowers the sensitivity for RSV case detection among young children hospitalized with an ALRTI and likely underestimates its burden.
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19.
  • Wang, Xin, et al. (author)
  • Global burden of respiratory infections associated with seasonal influenza in children under 5 years in 2018 : a systematic review and modelling study
  • 2020
  • In: The Lancet Global Health. - : Elsevier. - 2214-109X. ; 8:4, s. E497-E510
  • Research review (peer-reviewed)abstract
    • Background: Seasonal influenza virus is a common cause of acute lower respiratory infection (ALRI) in ung children. In 2008, we estimated that 20 million influenza-virus-associated ALRI and 1 million fluenza-virus-associated severe ALRI occurred in children under 5 years globally. Despite this bstantial burden, only a few low-income and middle-income countries have adopted routine influenza ccination policies for children and, where present, these have achieved only low or unknown levels of ccine uptake. Moreover, the influenza burden might have changed due to the emergence and rculation of influenza A/H1N1pdm09. We aimed to incorporate new data to update estimates of the obal number of cases, hospital admissions, and mortality from influenza-virus-associated respiratory fections in children under 5 years in 2018.Methods: We estimated the regional and global burden of influenza-associated respiratory infections in ildren under 5 years from a systematic review of 100 studies published between Jan 1, 1995, and Dec , 2018, and a further 57 high-quality unpublished studies. We adapted the Newcastle-Ottawa Scale to sess the risk of bias. We estimated incidence and hospitalisation rates of influenza-virus-associated spiratory infections by severity, case ascertainment, region, and age. We estimated in-hospital deaths om influenza virus ALRI by combining hospital admissions and in-hospital case-fatality ratios of fluenza virus ALRI. We estimated the upper bound of influenza virus-associated ALRI deaths based on e number of in-hospital deaths, US paediatric influenza-associated death data, and population-based ildhood all-cause pneumonia mortality data in six sites in low-income and lower-middle-income untries.Findings: In 2018, among children under 5 years globally, there were an estimated 109.5 million fluenza virus episodes (uncertainty range [UR] 63.1-190.6), 10.1 million influenza-virus-associated ALRI ses (6.8-15.1); 870 000 influenza-virus-associated ALRI hospital admissions (543 000-1 415 000), 15 300 -hospital deaths (5800-43 800), and up to 34 800 (13 200-97 200) overall influenza-virus-associated ALRI deaths. Influenza virus accounted for 7% of ALRI cases, 5% of ALRI hospital admissions, and 4% of ALRI deaths in children under 5 years. About 23% of the hospital admissions and 36% of the in-hospital deaths were in infants under 6 months. About 82% of the in-hospital deaths occurred in low-income and lower-middle-income countries.Interpretation: A large proportion of the influenza-associated burden occurs among young infants and in low-income and lower middle-income countries. Our findings provide new and important evidence for maternal and paediatric influenza immunisation, and should inform future immunisation policy particularly in low-income and middle-income countries. 
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20.
  • Wolter, Nicole, et al. (author)
  • High nasopharyngeal pneumococcal density, increased by viral coinfection, is associated with invasive pneumococcal pneumonia
  • 2014
  • In: Journal of Infectious Diseases. - : Oxford University Press. - 0022-1899 .- 1537-6613. ; 210:10, s. 1649-1657
  • Journal article (peer-reviewed)abstract
    • 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.
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