Publications by authors named "Jocelyn Moyes"

55 Publications

Housing Quality in a Rural and an Urban Settlement in South Africa.

Int J Environ Res Public Health 2021 Feb 24;18(5). Epub 2021 Feb 24.

Faculty of Health Sciences, School of Public Health, University of the Witwatersrand, Johannesburg 2193, South Africa.

During 2016 to 2018, a prospective household cohort study of influenza and respiratory syncytial virus community burden and transmission dynamics (the PHIRST study) was undertaken to examine the factors associated with influenza and other respiratory pathogen transmissions in South Africa. We collected information on housing conditions in the PHIRST study sites: Rural villages near Agincourt, Bushbuckridge Municipality, Mpumalanga Province, and urban Jouberton Township in North West Province. Survey data were collected from 159 and 167 study households in Agincourt and Jouberton, respectively. Multiple housing-related health hazards were identified in both sites, but particularly in Agincourt. In Agincourt, 75% (119/159) of households reported daily or weekly interruptions in water supply and 98% (154/159) stored drinking water in miscellaneous containers, compared to 1% (1/167) and 69% (115/167) of households in Jouberton. Fuels other than electricity (such as wood) were mainly used for cooking by 44% (70/159) and 7% (11/167) of Agincourt and Jouberton households, respectively; and 67% (106/159) of homes in Agincourt versus 47% (79/167) in Jouberton were located on unpaved roads, which is associated with the generation of dust and particulate matter. This study has highlighted housing conditions in Agincourt and Jouberton that are detrimental to health, and which may impact disease severity or transmission in South African communities.
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http://dx.doi.org/10.3390/ijerph18052240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956558PMC
February 2021

Influenza economic burden among potential target risk groups for immunization in South Africa, 2013-2015.

Vaccine 2020 10 24;38(45):7007-7014. Epub 2020 Sep 24.

Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa; School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. Electronic address:

Background: Data on influenza economic burden in risk groups for severe influenza are important to guide targeted influenza immunization, especially in resource-limited settings. However, this information is limited in low- and middle-income countries.

Methods: We estimated the cost (from a health system and societal perspective) and years of life lost (YLL) for influenza-associated illness in South Africa during 2013-2015 among (i) children aged 6-59 months, (ii) individuals aged 5-64 years with HIV, pulmonary tuberculosis (PTB) and selected underlying medical conditions (UMC), separately, (iii) pregnant women and (iv) individuals aged ≥65 years, using publicly available data and data collected through laboratory-confirmed influenza surveillance and costing studies. All costs were expressed in 2015 prices using the South Africa all-items Consumer Price Index.

Results: During 2013-2015, the mean annual cost of influenza-associated illness among the selected risk groups accounted for 52.1% ($140.9/$270.5 million) of the total influenza-associated illness cost (for the entire population of South Africa), 45.2% ($52.2/$115.5 million) of non-medically attended illness costs, 43.3% ($46.7/$107.9 million) of medically-attended mild illness costs and 89.3% ($42.0/$47.1 million) of medically-attended severe illness costs. The YLL among the selected risk groups accounted for 86.0% (262,069 /304,867 years) of the total YLL due to influenza-associated death.

Conclusion: In South Africa, individuals in risk groups for severe influenza accounted for approximately half of the total influenza-associated illness cost but most of the cost of influenza-associated medically attended severe illness and YLL. This study provides the foundation for future studies on the cost-effectiveness of influenza immunization among risk groups.
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http://dx.doi.org/10.1016/j.vaccine.2020.09.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581517PMC
October 2020

Influenza disease burden among potential target risk groups for immunization in South Africa, 2013-2015.

Vaccine 2020 06 7;38(27):4288-4297. Epub 2020 May 7.

Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa; School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. Electronic address:

Background: Data on influenza burden in risk groups for severe influenza are important to guide targeted influenza immunization, especially in resource limited settings. However, this information is limited overall and in particular in low- and middle-income countries. We sought to assess the mean annual national burden of medically and non-medically attended influenza-associated mild, severe-non-fatal and fatal illness among potential target groups for influenza immunization in South Africa during 2013-2015.

Methods: We used published mean national annual estimates of mild, severe-non-fatal, and fatal influenza-associated illness in South Africa during 2013-2015 and estimated the number of such illnesses occurring among the following risk groups: (i) children aged 6-59 months; (ii) individuals aged 5-64 years with HIV, and/or pulmonary tuberculosis (PTB), and/or selected underlying medical conditions (UMC); (iii) pregnant women; and (iv) individuals aged ≥65 years. We also estimated the number of individuals among the same risk groups in the population.

Results: During 2013-2015, individuals in the selected risk groups accounted for 45.3% (24,569,328/54,086,144) of the population and 43.5% (4,614,763/10,598,138), 86.8% (111,245/128,173) and 94.5% (10,903/11,536) of the mean annual estimated number of influenza-associated mild, severe-non-fatal and fatal illness episodes, respectively. The rates of influenza-associated illness were highest in children aged 6-59 months (23,983 per 100,000 population) for mild illness, in pregnant women (930 per 100,000 population) for severe-non-fatal illness and in individuals aged ≥65 years (138 per 100,000 population) for fatal illness.

Conclusion: Influenza immunization of the selected risk groups has the potential to prevent a substantial number of influenza-associated severe illness. Nonetheless, because of the high number of individuals at risk, South Africa, due to financial resources constrains, may need to further prioritize interventions among risk populations. Cost-burden and cost-effectiveness estimates may assist with further prioritization.
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http://dx.doi.org/10.1016/j.vaccine.2020.04.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870979PMC
June 2020

Human respiratory syncytial virus and influenza seasonality patterns-Early findings from the WHO global respiratory syncytial virus surveillance.

Influenza Other Respir Viruses 2020 11 12;14(6):638-646. Epub 2020 Mar 12.

Global Influenza Programme, World Health Organization, Geneva, Switzerland.

Background: Human respiratory syncytial virus (RSV) causes illnesses among all age groups and presents a burden to healthcare services. To better understand the epidemiology and seasonality of RSV in different geographical areas, the World Health Organization (WHO) coordinated a pilot initiative to access the feasibility of establishing RSV surveillance using the existing Global Influenza Surveillance and Response System (GISRS) platform.

Objectives: To describe and compare RSV and influenza seasonality in countries in the northern andsouthern temperate, and tropics during the period January 2017 to April 2019.

Methods: Fourteen countries in six WHO regions participating in the GISRS were invited for the pilot. Hospitalized patients presenting with severe acute respiratory illness (SARI), SARI without fever and outpatients presenting with acute respiratory illness (ARI) were enrolled from January 2017 to April 2019. The expected minimum sample size was 20 samples per week, year-round, per country. Real-time RT-PCR was used to detect RSV and influenza viruses. Results were uploaded to the WHO FluMart platform.

Results: Annual seasonality of RSV was observed in all countries, which overlapped to a large extent with the influenza activity. In countries, in temperate regions RSV peaked in the autumn/winter months. In Egypt, a subtropical country, RSV activity peaked in the cooler season. In the tropical regions, RSV peaked during the rainy seasons.

Conclusion: Early findings from the WHO RSV surveillance pilot based on the GISRS suggest annual seasonal patterns for of RSV circulation that overlap with influenza. RSV surveillance needs to be continued for several more seasons to establish seasonality patterns to inform prevention and control strategies.
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http://dx.doi.org/10.1111/irv.12726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578323PMC
November 2020

Approaches to use the WHO respiratory syncytial virus surveillance platform to estimate disease burden.

Influenza Other Respir Viruses 2020 11 8;14(6):615-621. Epub 2019 Oct 8.

Global Influenza Program, World Health Organization, Geneva, Switzerland.

The World Health Organization (WHO) recently completed the first phase of a RSV surveillance pilot study in fourteen countries (two to three in each WHO region) building on the Global Influenza Surveillance and Response System (GISRS). This active surveillance strategy had several objectives including understanding RSV-related health burden in a variety of settings. A range of approaches can be used to estimate disease burden; most approaches could not be applied by participating countries in the WHO surveillance pilot. This article provides the recommendations made by WHO for strengthening and expanding the scope of the RSV surveillance in the next phase to enable burden estimation.
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http://dx.doi.org/10.1111/irv.12667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578280PMC
November 2020

A cost-effectiveness analysis of antenatal influenza vaccination among HIV-infected and HIV-uninfected pregnant women in South Africa.

Vaccine 2019 10 28;37(46):6874-6884. Epub 2019 Sep 28.

Department of Health Policy and Management, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.

Background: Pregnant women and infants are at increased risk of severe disease from influenza. Antenatal influenza vaccination is safe and can reduce the risk of illness for women and their infants. We evaluated for South Africa the health effects of antenatal influenza vaccination among pregnant women and their infants aged <6 months old and assessed its cost-effectiveness.

Methods: We constructed a decision tree model to simulate the population of pregnant women and infants aged <6 months in South Africa using TreeAge Pro Suite 2015. The model evaluated the change in societal costs and outcomes associated with a vaccination campaign that prioritized HIV-infected over HIV-uninfected pregnant women compared with no vaccination. We also examined the impacts of a campaign without prioritization. Upper and lower 90% uncertainty intervals (90% UI) were generated using probabilistic sensitivity analysis on 10000 Monte Carlo simulations. The cost-effectiveness threshold was set to the 2015 per capita gross domestic product of South Africa, US$5724.

Results: Antenatal vaccination with prioritization averted 9070 (90% UI: 7407-11217) total cases of influenza among pregnant women and infants, including 411 (90% UI: 305-546) hospitalizations and 30 (90% UI: 22-40) deaths. This corresponds to an averted fraction of 13.5% (90% UI: 9.0-20.5%). Vaccinating without prioritization averted 7801 (90% UI: 6465-9527) cases of influenza, including 335 (90% UI: 254-440) hospitalizations and 24 (90% UI: 18-31) deaths. This corresponds to an averted fraction of 11.6% (90% UI: 7.8-17.4%). Vaccinating the cohort of pregnant women with prioritization had societal cost of $4689 (90% UI: $3128-$7294) per Quality Adjusted Life Year (QALY) gained while vaccinating without prioritization had a cost of $5924 (90% UI: $3992-$9056) per QALY.

Conclusions: Antenatal influenza vaccination campaigns in South Africa would reduce the impact of influenza and could be cost-effective.
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http://dx.doi.org/10.1016/j.vaccine.2019.09.059DOI Listing
October 2019

Influenza and tuberculosis co-infection: A systematic review.

Influenza Other Respir Viruses 2020 01 30;14(1):77-91. Epub 2019 Sep 30.

Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA, USA.

Introduction: There are limited data on risk of severe disease or outcomes in patients with influenza and pulmonary tuberculosis (PTB) co-infection compared to those with single infection.

Methods: We conducted a systematic review of published literature on the interaction of influenza viruses and PTB. Studies were eligible for inclusion if they presented data on prevalence, disease association, presentation or severity of laboratory-confirmed influenza among clinically diagnosed or laboratory-confirmed PTB cases. We searched eight databases from inception until December 2018. Summary characteristics of each study were extracted, and a narrative summary was presented. Cohort or case-control studies were assessed for potential bias using the Newcastle-Ottawa scale.

Results: We assessed 5154 abstracts, reviewed 146 manuscripts and included 19 studies fulfilling selection criteria (13 human and six animal). Of seven studies reporting on the possible effect of the underlying PTB disease in patients with influenza, three of four analytical studies reported no association with disease severity of influenza infection in those with PTB, whilst one study reported PTB as a risk factor for influenza-associated hospitalization. An association between influenza infection and PTB disease was found in three of five analytical studies; whereas the two other studies reported a high frequency of PTB disease progression and complications among patients with seasonal influenza co-infection.

Conclusion: Human analytical studies of an association between co-infection and severe influenza- or PTB-associated disease or increased prevalence of influenza co-infection in individuals' hospitalized for PTB were not conclusive. Data are limited from large, high-quality, analytical epidemiological studies with laboratory-confirmed endpoints.
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http://dx.doi.org/10.1111/irv.12670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928059PMC
January 2020

The performance of different case definitions for severe influenza surveillance among HIV-infected and HIV-uninfected children aged <5 years in South Africa, 2011-2015.

PLoS One 2019 19;14(9):e0222294. Epub 2019 Sep 19.

Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.

In 2014, the World Health Organization (WHO) proposed a new severe influenza surveillance case definition, which has not been evaluated in a high human immunodeficiency virus (HIV) prevalence setting. Our study aimed to assess the performance of this proposed case definition in identifying influenza among HIV-uninfected and HIV-infected children aged <5 years in South Africa. We prospectively enrolled children aged <5 years hospitalised with physician-diagnosed lower respiratory tract infection (LRTI) at two surveillance sites from January 2011 to December 2015. Epidemiologic and clinical data were collected. We tested nasopharyngeal aspirates for influenza using reverse transcription polymerase chain reaction. We used logistic regression to assess factors associated with influenza positivity among HIV-infected and HIV-uninfected children. We calculated sensitivity and specificity for different signs and symptoms and combinations of these for laboratory-confirmed influenza. We enrolled 2,582 children <5 years of age with LRTI of whom 87% (2,257) had influenza and HIV results, of these 14% (318) were HIV-infected. The influenza detection rate was 5% (104/1,939) in HIV-uninfected and 5% (16/318) in HIV-infected children. Children with measured fever (≥38°C) were two times more likely to test positive for influenza than those without measured fever among the HIV-uninfected (OR 2.2, 95% Confidence Interval (CI) 1.5-3.4; p<0.001). No significant association was observed between fever and influenza infection among HIV-infected children. Cough alone had sensitivity of 95% (95% CI 89-98%) in HIV-uninfected and of 100% (95% CI 79-100%) in HIV-infected children but low specificity: 7% (95% CI 6-8%) and 6% (95% CI 3-9%) in HIV-uninfected and HIV-infected children, respectively. The WHO post-2014 case definition for severe acute respiratory illness (SARI-an acute respiratory infection with history of fever or measured fever of ≥ 38°C and cough; with onset within the last ten days and requires hospitalization), had a sensitivity of 66% (95% CI 56-76%) and specificity of 46% (95% CI 44-48%) among HIV-uninfected and a sensitivity of 63% (95% CI 35-84%) and a specificity of 42% (95% CI 36-48%) among HIV-infected children. The sensitivity and specificity of the WHO post-2014 case definition for SARI were similar among HIV-uninfected and HIV-infected children. Our findings support the adoption of the 2014 WHO case definition for children aged <5 years irrespective of HIV infection status.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0222294PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752836PMC
March 2020

Health and economic burden of influenza-associated illness in South Africa, 2013-2015.

Influenza Other Respir Viruses 2019 09 11;13(5):484-495. Epub 2019 Jun 11.

Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.

Background: Economic burden estimates are essential to guide policy-making for influenza vaccination, especially in resource-limited settings.

Methods: We estimated the cost, absenteeism, and years of life lost (YLL) of medically and non-medically attended influenza-associated mild and severe respiratory, circulatory and non-respiratory/non-circulatory illness in South Africa during 2013-2015 using a modified version of the World Health Organization (WHO) worksheet based tool for estimating the economic burden of seasonal influenza. Additionally, we restricted the analysis to influenza-associated severe acute respiratory illness (SARI) and influenza-like illness (ILI; subsets of all-respiratory illnesses) as suggested in the WHO manual.

Results: The estimated mean annual cost of influenza-associated illness was $270.5 million, of which $111.3 million (41%) were government-incurred costs, 40.7 million (15%) were out-of-pocket expenses, and $118.4 million (44%) were indirect costs. The cost of influenza-associated medically attended mild illness ($107.9 million) was 2.3 times higher than that of severe illness ($47.1 million). Influenza-associated respiratory illness costs ($251.4 million) accounted for 93% of the total cost. Estimated absenteeism and YLL were 13.2 million days and 304 867 years, respectively. Among patients with influenza-associated WHO-defined ILI or SARI, the costs ($95.3 million), absenteeism (4.5 million days), and YLL (65 697) were 35%, 34%, and 21% of the total economic and health burden of influenza.

Conclusion: The economic burden of influenza-associated illness was substantial from both a government and a societal perspective. Models that limit estimates to those obtained from patients with WHO-defined ILI or SARI substantially underestimated the total economic and health burden of influenza-associated illness.
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http://dx.doi.org/10.1111/irv.12650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692552PMC
September 2019

The Impact of Human Immunodeficiency Virus Exposure on Respiratory Syncytial Virus-associated Severe Respiratory Illness in South African Infants, 2011-2016.

Clin Infect Dis 2019 11;69(12):2208-2211

Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.

From 2011 through 2016, we conducted surveillance for severe respiratory illness in infants. Human immunodeficiency virus exposure significantly increased the risk of respiratory syncytial virus (RSV)-associated hospitalization in infants aged <5 months. More than 60% of RSV-associated hospitalizations occurred in the first 4 months of life and may be preventable through maternal vaccination or birth-dose monoclonal antibody.
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http://dx.doi.org/10.1093/cid/ciz288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934254PMC
November 2019

The Impact of Influenza and Tuberculosis Interaction on Mortality Among Individuals Aged ≥15 Years Hospitalized With Severe Respiratory Illness in South Africa, 2010-2016.

Open Forum Infect Dis 2019 Mar 19;6(3):ofz020. Epub 2019 Mar 19.

Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.

Background: Data on the prevalence and impact of influenza-tuberculosis coinfection on clinical outcomes from high-HIV and -tuberculosis burden settings are limited. We explored the impact of influenza and tuberculosis coinfection on mortality among hospitalized adults with lower respiratory tract infection (LRTI).

Methods: We enrolled patients aged ≥15 years admitted with physician-diagnosed LRTI or suspected tuberculosis at 2 hospitals in South Africa from 2010 to 2016. Combined nasopharyngeal and oropharyngeal swabs were tested for influenza and 8 other respiratory viruses. Tuberculosis testing of sputum included smear microscopy, culture, and/or Xpert MTB/Rif.

Results: Among 6228 enrolled individuals, 4253 (68%) were tested for both influenza and tuberculosis. Of these, the detection rate was 6% (239/4253) for influenza, 26% (1092/4253) for tuberculosis, and 77% (3113/4053) for HIV. One percent (42/4253) tested positive for both influenza and tuberculosis. On multivariable analysis, among tuberculosis-positive patients, factors independently associated with death were age group ≥65 years compared with 15-24 years (adjusted odds ratio [aOR], 3.6; 95% confidence interval [CI], 1.2-11.0) and influenza coinfection (aOR, 2.3; 95% CI, 1.02-5.2). Among influenza-positive patients, laboratory-confirmed tuberculosis was associated with an increased risk of death (aOR, 4.5; 95% CI, 1.5-13.3). Coinfection with other respiratory viruses was not associated with increased mortality in patients positive for tuberculosis (OR, 0.7; 95% CI, 0.4-1.1) or influenza (OR, 1.6; 95% CI, 0.4-5.6).

Conclusions: Tuberculosis coinfection is associated with increased mortality in individuals with influenza, and influenza coinfection is associated with increased mortality in individuals with tuberculosis. These data may inform prioritization of influenza vaccines or antivirals for tuberculosis patients and inform tuberculosis testing guidelines for patients with influenza.
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http://dx.doi.org/10.1093/ofid/ofz020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6424478PMC
March 2019

The Fraction of Rhinovirus Detections Attributable to Mild and Severe Respiratory Illness in a Setting of High Human Immunodeficiency Virus Prevalence, South Africa, 2013-2015.

J Infect Dis 2019 05;219(11):1697-1704

Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg.

Background: The association of rhinovirus (RV) detection to illness is poorly understood.

Methods: We enrolled case patients hospitalized with severe respiratory illness (SRI) at 2 hospitals and outpatients with influenza-like illness (ILI) and asymptomatic individuals (controls) from 2 affiliated clinics during 2013-2015. We compared the RV prevalence among ILI and SRI cases to those of controls stratified by human immunodeficiency virus (HIV) serostatus using penalized logistic regression. The attributable fraction (AF) was calculated.

Results: During 2013-2015, RV was detected in 17.4% (368/2120), 26.8% (979/3654), and 23.0% (1003/4360) of controls, ILI cases, and SRI cases, respectively. The RV AF (95% confidence interval) was statistically significant among children aged <5 years (ILI: 44.6% [30.7%-55.7%] and SRI: 50.3% [38.6%-59.9%]; P < .001) and individuals aged ≥5 years (ILI: 62.9% [54.4%-69.8%] and SRI: 51.3% [38.7%-61.3%]; P < .001) as well as among HIV-infected (ILI: 59.9% [45.8%-70.3%] and SRI: 39.8% [22.3%-53.3%]; P < .001) and HIV-uninfected (ILI: 53.6% [44.7%-61.1%] and SRI: 55.3% [45.6%-63.2%]; P < .001) individuals.

Conclusions: Although RV detection was common among controls, it was also associated with a substantial proportion of clinical illness across age groups, irrespective of HIV status.
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http://dx.doi.org/10.1093/infdis/jiy725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804373PMC
May 2019

Quantifying How Different Clinical Presentations, Levels of Severity, and Healthcare Attendance Shape the Burden of Influenza-associated Illness: A Modeling Study From South Africa.

Clin Infect Dis 2019 08;69(6):1036-1048

Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.

Background: Burden estimates of medically and nonmedically attended influenza-associated illness across syndromes and levels of severity are lacking.

Methods: We estimated the national burden of medically and nonmedically attended influenza-associated illness among individuals with different clinical presentations (all-respiratory, all-circulatory, and nonrespiratory/noncirculatory) and levels of severity (mild, fatal, and severe, nonfatal) using a combination of case-based (from laboratory-confirmed influenza surveillance) and ecological studies, as well as data from healthcare utilization surveys in South Africa during 2013-2015. In addition, we compared estimates of medically attended influenza-associated respiratory illness, obtained from case-based and ecological studies. Rates were reported per 100 000 individuals in the population.

Results: The estimated mean annual number of influenza-associated illness episodes was 10 737 847 (19.8% of 54 096 705 inhabitants). Of these episodes, 10 598 138 (98.7%) were mild, 128 173 (1.2%) were severe, nonfatal, and 11 536 (0.1%) were fatal. There were 2 718 140 (25.6%) mild, 56 226 (43.9%) severe, nonfatal, and 4945 (42.8%) medically attended should be after fatal episodes. Influenza-associated respiratory illness accounted for 99.2% (10 576 146) of any mild, 65.5% (83 941) of any severe, nonfatal, and 33.7% (3893) of any fatal illnesses. Ecological and case-based estimates of medically attended, influenza-associated, respiratory mild (rates: ecological, 1778.8, vs case-based, 1703.3; difference, 4.4%), severe, nonfatal (rates: ecological, 88.6, vs case-based, 75.3; difference, 15.0%), and fatal (rates: ecological, 3.8, vs case-based, 3.5; difference, 8.4%) illnesses were similar.

Conclusions: There was a substantial burden of influenza-associated symptomatic illness, including severe, nonfatal and fatal illnesses, and a large proportion was nonmedically attended. Estimates, including only influenza-associated respiratory illness, substantially underestimated influenza-associated, severe, nonfatal and fatal illnesses. Ecological and case-based estimates were found to be similar for the compared categories.
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http://dx.doi.org/10.1093/cid/ciy1017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804385PMC
August 2019

The Role of Human Immunodeficiency Virus in Influenza- and Respiratory Syncytial Virus-associated Hospitalizations in South African Children, 2011-2016.

Clin Infect Dis 2019 02;68(5):773-780

Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service.

Background: Data describing influenza- or respiratory syncytial virus (RSV)-associated hospitalized illness in children aged <5 years in Africa are limited.

Methods: During 2011-2016, we conducted surveillance for severe respiratory illness (SRI) in children aged <5 years in 3 South African hospitals. Nasopharyngeal aspirates were tested for influenza and RSV using real-time reverse transcription polymerase chain reaction. We estimated rates of influenza- and RSV-associated hospitalized SRI by human immunodeficiency virus (HIV) status and compared children who tested positive for influenza vs RSV using multivariable penalized logistic regression.

Results: Among 3650 hospitalized children, 203 (5.6%) tested positive for influenza viruses, 874 (23.9%) for RSV, and 19 (0.5%) for both. The median age of children hospitalized with influenza was 13.9 months vs 4.4 months for RSV (P < .01). Annual influenza-associated hospitalization rates per 100000 were highest among infants aged 6-11 months (545; 95% confidence interval [CI], 409-703), while RSV-associated hospitalization rates were highest in infants aged 0-2 months (6593; 95% CI, 5947-7217). HIV exposure was associated with increased incidence of influenza- and RSV-associated hospitalization in infants aged 0-5 months, with relative risk (RR) 2.2 (95% CI, 1.4-3.4) and 1.4 (95% CI, 1.3-1.6), respectively. HIV infection was associated with increased incidence of influenza- and RSV-associated hospitalization in all age groups; RR 2.7 (95% CI, 2.0-3.5) and 3.8 (95% CI, 3.1-4.8), respectively.

Conclusions: Influenza- and RSV-associated hospitalizations are common among South African infants. HIV infection and HIV exposure in infants increase risk of influenza- and RSV-associated hospitalization.
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http://dx.doi.org/10.1093/cid/ciy532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6432774PMC
February 2019

Performance of Surveillance Case Definitions in Detecting Respiratory Syncytial Virus Infection Among Young Children Hospitalized With Severe Respiratory Illness-South Africa, 2009-2014.

J Pediatric Infect Dis Soc 2019 Sep;8(4):325-333

Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, Johannesburg, South Africa.

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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http://dx.doi.org/10.1093/jpids/piy055DOI Listing
September 2019

The cost-effectiveness of trivalent and quadrivalent influenza vaccination in communities in South Africa, Vietnam and Australia.

Vaccine 2018 02 17;36(7):997-1007. Epub 2018 Jan 17.

School of Computer Science and Software Engineering, University of Western Australia, Perth, Australia. Electronic address:

Background: To inform national healthcare authorities whether quadrivalent influenza vaccines (QIVs) provide better value for money than trivalent influenza vaccines (TIVs), we assessed the cost-effectiveness of TIV and QIV in low-and-middle income communities based in South Africa and Vietnam and contrasted these findings with those from a high-income community in Australia.

Methods: Individual based dynamic simulation models were interfaced with a health economic analysis model to estimate the cost-effectiveness of vaccinating 15% of the population with QIV or TIV in each community over the period 2003-2013. Vaccination was prioritized for HIV-infected individuals, before elderly aged 65+ years and young children. Country or region-specific data on influenza-strain circulation, clinical outcomes and costs were obtained from published sources. The societal perspective was used and outcomes were expressed in International$ (I$) per quality-adjusted life-year (QALY) gained.

Results: When compared with TIV, we found that QIV would provide a greater reduction in influenza-related morbidity in communities in South Africa and Vietnam as compared with Australia. The incremental cost-effectiveness ratio of QIV versus TIV was estimated at I$4183/QALY in South Africa, I$1505/QALY in Vietnam and I$80,966/QALY in Australia.

Conclusions: The cost-effectiveness of QIV varied between communities due to differences in influenza epidemiology, comorbidities, and unit costs. Whether TIV or QIV is the most cost-effective alternative heavily depends on influenza B burden among subpopulations targeted forvaccination in addition to country-specific willingness-to-pay thresholds and budgetary impact.
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http://dx.doi.org/10.1016/j.vaccine.2017.12.073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805858PMC
February 2018

The effects of the attributable fraction and the duration of symptoms on burden estimates of influenza-associated respiratory illnesses in a high HIV prevalence setting, South Africa, 2013-2015.

Influenza Other Respir Viruses 2018 05 1;12(3):360-373. Epub 2018 Feb 1.

Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.

Background: The attributable fraction of influenza virus detection to illness (INF-AF) and the duration of symptoms as a surveillance inclusion criterion could potentially have substantial effects on influenza disease burden estimates.

Methods: We estimated rates of influenza-associated influenza-like illness (ILI) and severe acute (SARI-10) or chronic (SCRI-10) respiratory illness (using a symptom duration cutoff of ≤10 days) among HIV-infected and HIV-uninfected patients attending 3 hospitals and 2 affiliated clinics in South Africa during 2013-2015. We calculated the unadjusted and INF-AF-adjusted rates and relative risk (RR) due to HIV infection. Rates were expressed per 100 000 population.

Results: The estimated mean annual unadjusted rates of influenza-associated illness were 1467.7, 50.3, and 27.4 among patients with ILI, SARI-10, and SCRI-10, respectively. After adjusting for the INF-AF, the percent reduction in the estimated rates was 8.9% (rate: 1336.9), 11.0% (rate: 44.8), and 16.3% (rate: 22.9) among patients with ILI, SARI-10, and SCRI-10, respectively. HIV-infected compared to HIV-uninfected individuals experienced a 2.3 (95% CI: 2.2-2.4)-, 9.7 (95% CI: 8.0-11.8)-, and 10.0 (95% CI: 7.9-12.7)-fold increased risk of influenza-associated illness among patients with ILI, SARI-10, and SCRI-10, respectively. Overall 34% of the estimated influenza-associated hospitalizations had symptom duration of >10 days; 8% and 44% among individuals aged <5 and ≥5 years, respectively.

Conclusion: The marginal differences between unadjusted and INF-AF-adjusted rates are unlikely to affect policies on prioritization of interventions. HIV-infected individuals experienced an increased risk of influenza-associated illness and may benefit more from annual influenza immunization. The use of a symptom duration cutoff of ≤10 days may underestimate influenza-associated disease burden, especially in older individuals.
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http://dx.doi.org/10.1111/irv.12529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5907815PMC
May 2018

Global respiratory syncytial virus-associated mortality in young children (RSV GOLD): a retrospective case series.

Lancet Glob Health 2017 10;5(10):e984-e991

Department of Paediatric Infectious Diseases and Immunology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, Netherlands; ReSViNET Respiratory Syncytial Virus Network, Utrecht, Netherlands. Electronic address:

Background: Respiratory syncytial virus (RSV) infection is an important cause of pneumonia mortality in young children. However, clinical data for fatal RSV infection are scarce. We aimed to identify clinical and socioeconomic characteristics of children aged younger than 5 years with RSV-related mortality using individual patient data.

Methods: In this retrospective case series, we developed an online questionnaire to obtain individual patient data for clinical and socioeconomic characteristics of children aged younger than 5 years who died with community-acquired RSV infection between Jan 1, 1995, and Oct 31, 2015, through leading research groups for child pneumonia identified through a comprehensive literature search and existing research networks. For the literature search, we searched PubMed for articles published up to Feb 3, 2015, using the key terms "RSV", "respiratory syncytial virus", or "respiratory syncytial viral" combined with "mortality", "fatality", "death", "died", "deaths", or "CFR" for articles published in English. We invited researchers and clinicians identified to participate between Nov 1, 2014, and Oct 31, 2015. We calculated descriptive statistics for all variables.

Findings: We studied 358 children with RSV-related in-hospital death from 23 countries across the world, with data contributed from 31 research groups. 117 (33%) children were from low-income or lower middle-income countries, 77 (22%) were from upper middle-income countries, and 164 (46%) were from high-income countries. 190 (53%) were male. Data for comorbidities were missing for some children in low-income and middle-income countries. Available data showed that comorbidities were present in at least 33 (28%) children from low-income or lower middle-income countries, 36 (47%) from upper middle-income countries, and 114 (70%) from high-income countries. Median age for RSV-related deaths was 5·0 months (IQR 2·3-11·0) in low-income or lower middle-income countries, 4·0 years (2·0-10·0) in upper middle-income countries, and 7·0 years (3·6-16·8) in high-income countries.

Interpretation: This study is the first large case series of children who died with community-acquired RSV infection. A substantial proportion of children with RSV-related death had comorbidities. Our results show that perinatal immunisation strategies for children aged younger than 6 months could have a substantial impact on RSV-related child mortality in low-income and middle-income countries.

Funding: Bill & Melinda Gates Foundation.
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http://dx.doi.org/10.1016/S2214-109X(17)30344-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5599304PMC
October 2017

The Burden and Clinical Presentation of Pulmonary Tuberculosis in Adults With Severe Respiratory Illness in a High Human Immunodeficiency Virus Prevalence Setting, 2012-2014.

Open Forum Infect Dis 2017 7;4(3):ofx116. Epub 2017 Aug 7.

Centres for Respiratory Diseases and Meningitis and.

Background: Understanding the burden and clinical presentation of tuberculosis in patients with severe respiratory illness (SRI) has important implications for anticipating treatment requirements.

Methods: Hospitalized patients aged ≥15 years with SRI at 2 public teaching hospitals in periurban areas in 2 provinces (Edendale Hospital in Pietermaritzburg, KwaZulu-Natal Province and Tshepong Hospital in Klerksdorp, North West Province) were enrolled prospectively from 2012 to 2014. Tuberculosis testing included smear microscopy, culture, or Xpert MTB/Rif.

Results: We enrolled 2486 individuals with SRI. Of these, 2097 (84%) were tested for tuberculosis, 593 (28%) were positive. Tuberculosis detection rate was 18% (133 of 729) in individuals with acute (≤14 days) presentation and 34% (460 of 1368) in those with chronic (>14 days) presentation. Among laboratory-confirmed tuberculosis cases, those with acute presentation were less likely to present with cough (88% [117 of 133] vs 97% [447 of 460]; ajusted odds ratio [aOR] = 0.2, 95% confidence interval [CI] = 0.1-0.5), night sweats (57% [75 of 132] vs 73% [337 of 459]; aOR = 0.4, 95% CI = 0.3-0.7), or be started on tuberculosis treatment on admission (63% [78 of 124] vs 81% [344 of 423]; aOR = 0.4, 95% CI = 0.3-0.7), but they were more likely to be coinfected with pneumococcus (13% [16 of 124] vs 6% [26 of 411]; aOR 2.3, 95% CI 1.3-5.3) than patients with chronic presentation. Annual incidence of acute and chronic tuberculosis-associated SRI per 100000 population was 28 (95% CI = 22-39) and 116 (95% CI = 104-128), respectively.

Conclusions: In this setting, tuberculosis, including acute presentation, is common in patients hospitalized with SRI.
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http://dx.doi.org/10.1093/ofid/ofx116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5570023PMC
August 2017

Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study.

Authors:
Ting Shi David A McAllister Katherine L O'Brien Eric A F Simoes Shabir A Madhi Bradford D Gessner Fernando P Polack Evelyn Balsells Sozinho Acacio Claudia Aguayo Issifou Alassani Asad Ali Martin Antonio Shally Awasthi Juliet O Awori Eduardo Azziz-Baumgartner Henry C Baggett Vicky L Baillie Angel Balmaseda Alfredo Barahona Sudha Basnet Quique Bassat Wilma Basualdo Godfrey Bigogo Louis Bont Robert F Breiman W Abdullah Brooks Shobha Broor Nigel Bruce Dana Bruden Philippe Buchy Stuart Campbell Phyllis Carosone-Link Mandeep Chadha James Chipeta Monidarin Chou Wilfrido Clara Cheryl Cohen Elizabeth de Cuellar Duc-Anh Dang Budragchaagiin Dash-Yandag Maria Deloria-Knoll Mukesh Dherani Tekchheng Eap Bernard E Ebruke Marcela Echavarria Carla Cecília de Freitas Lázaro Emediato Rodrigo A Fasce Daniel R Feikin Luzhao Feng Angela Gentile Aubree Gordon Doli Goswami Sophie Goyet Michelle Groome Natasha Halasa Siddhivinayak Hirve Nusrat Homaira Stephen R C Howie Jorge Jara Imane Jroundi Cissy B Kartasasmita Najwa Khuri-Bulos Karen L Kotloff Anand Krishnan Romina Libster Olga Lopez Marilla G Lucero Florencia Lucion Socorro P Lupisan Debora N Marcone John P McCracken Mario Mejia Jennifer C Moisi Joel M Montgomery David P Moore Cinta Moraleda Jocelyn Moyes Patrick Munywoki Kuswandewi Mutyara Mark P Nicol D James Nokes Pagbajabyn Nymadawa Maria Tereza da Costa Oliveira Histoshi Oshitani Nitin Pandey Gláucia Paranhos-Baccalà Lia N Phillips Valentina Sanchez Picot Mustafizur Rahman Mala Rakoto-Andrianarivelo Zeba A Rasmussen Barbara A Rath Annick Robinson Candice Romero Graciela Russomando Vahid Salimi Pongpun Sawatwong Nienke Scheltema Brunhilde Schweiger J Anthony G Scott Phil Seidenberg Kunling Shen Rosalyn Singleton Viviana Sotomayor Tor A Strand Agustinus Sutanto Mariam Sylla Milagritos D Tapia Somsak Thamthitiwat Elizabeth D Thomas Rafal Tokarz Claudia Turner Marietjie Venter Sunthareeya Waicharoen Jianwei Wang Wanitda Watthanaworawit Lay-Myint Yoshida Hongjie Yu Heather J Zar Harry Campbell Harish Nair

Lancet 2017 Sep 7;390(10098):946-958. Epub 2017 Jul 7.

Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland, UK; Public Health Foundation of India, New Delhi, India. Electronic address:

Background: We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on RSV has yielded substantial new data from developing countries. With a considerably expanded dataset from a large international collaboration, we aimed to estimate the global incidence, hospital admission rate, and mortality from RSV-ALRI episodes in young children in 2015.

Methods: We estimated the incidence and hospital admission rate of RSV-associated ALRI (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions from a systematic review of studies published between Jan 1, 1995, and Dec 31, 2016, and unpublished data from 76 high quality population-based studies. We estimated the RSV-ALRI incidence for 132 developing countries using a risk factor-based model and 2015 population estimates. We estimated the in-hospital RSV-ALRI mortality by combining in-hospital case fatality ratios with hospital admission estimates from hospital-based (published and unpublished) studies. We also estimated overall RSV-ALRI mortality by identifying studies reporting monthly data for ALRI mortality in the community and RSV activity.

Findings: We estimated that globally in 2015, 33·1 million (uncertainty range [UR] 21·6-50·3) episodes of RSV-ALRI, resulted in about 3·2 million (2·7-3·8) hospital admissions, and 59 600 (48 000-74 500) in-hospital deaths in children younger than 5 years. In children younger than 6 months, 1·4 million (UR 1·2-1·7) hospital admissions, and 27 300 (UR 20 700-36 200) in-hospital deaths were due to RSV-ALRI. We also estimated that the overall RSV-ALRI mortality could be as high as 118 200 (UR 94 600-149 400). Incidence and mortality varied substantially from year to year in any given population.

Interpretation: Globally, RSV is a common cause of childhood ALRI and a major cause of hospital admissions in young children, resulting in a substantial burden on health-care services. About 45% of hospital admissions and in-hospital deaths due to RSV-ALRI occur in children younger than 6 months. An effective maternal RSV vaccine or monoclonal antibody could have a substantial effect on disease burden in this age group.

Funding: The Bill & Melinda Gates Foundation.
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http://dx.doi.org/10.1016/S0140-6736(17)30938-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5592248PMC
September 2017

Respiratory syncytial virus in adults with severe acute respiratory illness in a high HIV prevalence setting.

J Infect 2017 10 1;75(4):346-355. Epub 2017 Jul 1.

Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa; Medical Research Council: Respiratory and Meningeal Pathogens Research Unit and Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, Johannesburg, South Africa.

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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http://dx.doi.org/10.1016/j.jinf.2017.06.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5712433PMC
October 2017

Attributable Fraction of Influenza Virus Detection to Mild and Severe Respiratory Illnesses in HIV-Infected and HIV-Uninfected Patients, South Africa, 2012-2016.

Emerg Infect Dis 2017 07;23(7):1124-1132

The attributable fraction (AF) of influenza virus detection to illness has not been described for patients in different age groups or with different HIV infection statuses. We compared the age group-specific prevalence of influenza virus infection among patients with influenza-like illness (ILI) or severe acute or chronic respiratory illness (SARI and SCRI, respectively) with that among controls, stratified by HIV serostatus. The overall AF for influenza virus detection to illness was 92.6% for ILI, 87.4% for SARI, and 86.2% for SCRI. Among HIV-uninfected patients, the AF for all syndromes was highest among persons <1 and >65 years of age and lowest among persons 25-44 years of age; this trend was not observed among HIV-infected patients. Overall, influenza viruses when detected in patients with ILI, SARI, or SCRI are likely attributable to illness. This finding is particularly likely among children and the elderly irrespective of HIV serostatus and among HIV-infected persons irrespective of age.
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http://dx.doi.org/10.3201/eid2307.161959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5512492PMC
July 2017

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

Open Forum Infect Dis 2017 10;4(1):ofw262. Epub 2017 Feb 10.

Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.

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 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.
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http://dx.doi.org/10.1093/ofid/ofw262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414019PMC
February 2017

Severity of Respiratory Syncytial Virus Lower Respiratory Tract Infection With Viral Coinfection in HIV-Uninfected Children.

Clin Infect Dis 2017 02;64(4):443-450

Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg, South Africa.

Background: Molecular diagnostics enable sensitive detection of respiratory viruses, but their clinical significance remains unclear in pediatric lower respiratory tract infection (LRTI). We aimed to determine whether viral coinfections increased life-threatening disease in a large cohort.

Methods: Molecular testing was performed for respiratory viruses in nasopharyngeal aspirates collected from children aged <5 years within 24 hours of hospital admission during sentinel surveillance for severe acute respiratory illness (SARI) hospitalization conducted in South Africa during February 2009-December 2013. The primary outcome was life-threatening disease, defined as mechanical ventilation, intensive care unit admission, or death.

Results: Of 2322 HIV-uninfected children with respiratory syncytial virus (RSV)-associated LRTI, 1330 (57.3%) had RSV monoinfection, 38 (1.6%) had life-threatening disease, 575 (24.8%) had rhinovirus, 347 (14.9%) had adenovirus (ADV), and 30 (1.3%) had influenza virus. RSV and any other viral coinfection was not associated with severe disease, ADV coinfection had increased odds of life-threatening disease (adjusted OR, 3.4; 95% CI, 1.6-7.2; P = .001), and influenza coinfection had increased odds of life-threatening disease and prolonged length of stay (adjusted OR, 2.1; 95% CI, 1.0-4.5; P = .05) compared with RSV monoinfection.

Conclusions: RSV coinfection with any respiratory virus is not associated with more severe disease when compared to RSV alone in this study. However, increased life-threatening disease in RSV-ADV and RSV-influenza coinfection warrants further study.
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http://dx.doi.org/10.1093/cid/ciw756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5712444PMC
February 2017

Epidemiology of Acute Lower Respiratory Tract Infection in HIV-Exposed Uninfected Infants.

Pediatrics 2016 Apr 29;137(4). Epub 2016 Mar 29.

Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa; Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, Faculty of Health Sciences, Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases.

Background: Increased morbidity and mortality from lower respiratory tract infection (LRTI) has been suggested in HIV-exposed uninfected (HEU) children; however, the contribution of respiratory viruses is unclear. We studied the epidemiology of LRTI hospitalization in HIV-unexposed uninfected (HUU) and HEU infants aged <6 months in South Africa.

Methods: We prospectively enrolled hospitalized infants with LRTI from 4 provinces from 2010 to 2013. Using polymerase chain reaction, nasopharyngeal aspirates were tested for 10 viruses and blood for pneumococcal DNA. Incidence for 2010-2011 was estimated at 1 site with population denominators.

Results: We enrolled 3537 children aged <6 months. HIV infection and exposure status were determined for 2507 (71%), of whom 211 (8%) were HIV infected, 850 (34%) were HEU, and 1446 (58%) were HUU. The annual incidence of LRTI was elevated in HEU (incidence rate ratio [IRR] 1.4; 95% confidence interval [CI] 1.3-1.5) and HIV infected (IRR 3.8; 95% CI 3.3-4.5), compared with HUU infants. Relative incidence estimates were greater in HEU than HUU, for respiratory syncytial virus (RSV; IRR 1.4; 95% CI 1.3-1.6) and human metapneumovirus-associated (IRR 1.4; 95% CI 1.1-2.0) LRTI, with a similar trend observed for influenza (IRR 1.2; 95% CI 0.8-1.8). HEU infants overall, and those with RSV-associated LRTI had greater odds (odds ratio 2.1, 95% CI 1.1-3.8, and 12.2, 95% CI 1.7-infinity, respectively) of death than HUU.

Conclusions: HEU infants were more likely to be hospitalized and to die in-hospital than HUU, including specifically due to RSV. This group should be considered a high-risk group for LRTI.
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http://dx.doi.org/10.1542/peds.2015-3272DOI Listing
April 2016

Sapovirus prevalence in children less than five years of age hospitalised for diarrhoeal disease in South Africa, 2009-2013.

J Clin Virol 2016 May 19;78:82-8. Epub 2016 Mar 19.

National Institute for Communicable Diseases, Private Bag x4, Sandringham, 2131, South Africa.

Background: Although sapovirus (SaV) has been detected in 2.2-12.7% of gastroenteritis cases globally, there are limited data on SaV epidemiology.

Objectives: Describe the epidemiology, clinical characteristics and factors associated with SaV gastroenteritis in hospitalised children <5 years of age in South Africa.

Study Design: Between 2009 and 2013 during prospective diarrhoeal surveillance, stool specimens were collected from four sites and screened for SaVs and associated enteric pathogens using ELISA, microscopy, conventional and real-time PCR. Epidemiological and clinical data were compared in patients with or without SaV. Odds ratios were assessed by bivariate and stepwise multivariable logistic regression analysis.

Results: Sapoviruses were detected in 7.7% (238/3103) of children admitted to hospital and 11.4% (9/79) of deaths. Sapovirus was detected more commonly in children 19-24 months compared to<6months (aOR=2.3; p=0.018) and in males (aOR=2.0; p=0.001). Additional factors associated with SaV detection included residing with≥7 inhabitants compared to ≤3 (aOR=2.2; p=0.011) and concomitant norovirus infections (aOR=3.0; p=0.003). HIV-infected children with SaV were more likely to have bloody stools (aOR=16.8; p<0.001), low birth weight (<2.5kg; aOR=5.8; p=0.007) and live in environments without flush toilets (aOR=8.1; p=0.003) compared to HIV-uninfected children.

Conclusions: Sapoviruses, which are perceived to cause mild diarrhoea, were detected in hospitalised children and diarrhoeal deaths in South Africa. Determinants increasing the odds of SaV included overcrowding and concomitant infections while HIV-infected children with SaV displayed bloody stools, low birth weight and reduced access to proper sanitation. Mitigation strategies against SaV infections include improved sanitation.
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http://dx.doi.org/10.1016/j.jcv.2016.03.013DOI Listing
May 2016

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.

J Clin Virol 2016 Feb 19;75:21-6. Epub 2015 Dec 19.

Department of Medical Virology, University of Pretoria, South Africa; Global Disease Detection, Centers for Disease Control and Prevention, Pretoria, South Africa.

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.
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http://dx.doi.org/10.1016/j.jcv.2015.12.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5712432PMC
February 2016

Trivalent and quadrivalent influenza vaccination effectiveness in Australia and South Africa: results from a modelling study.

Influenza Other Respir Viruses 2016 07 8;10(4):324-32. Epub 2016 Feb 8.

Centre for Respiratory Disease and Meningitis, National Institute for Communicable Diseases, Johannesburg, South Africa.

Background: A modelling study was conducted to determine the effectiveness of trivalent (TIV) and quadrivalent (QIV) vaccination in South Africa and Australia.

Objectives: This study aimed to determine the potential benefits of alternative vaccination strategies which may depend on community-specific demographic and health characteristics.

Methods: Two influenza A and two influenza B strains were simulated using individual-based simulation models representing specific communities in South Africa and Australia over 11 years. Scenarios using TIV or QIV, with alternative prioritisation strategies and vaccine coverage levels, were evaluated using a country-specific health outcomes process.

Results: In South Africa, approximately 18% fewer deaths and hospitalisations would be expected to result from the use of QIV compared to TIV over the 11 modelled years (P = 0·031). In Australia, only 2% (P = 0·30) fewer deaths and hospitalisations would result. Vaccinating 2%, 5%, 15% or 20% of the population with TIV using a strategy of prioritising vulnerable age groups, including HIV-positive individuals, resulted in reductions in hospitalisations and mortality of at least 7%, 18%, 57% and 66%, respectively, in both communities.

Conclusions: The degree to which QIV can reduce health burden compared to TIV is strongly dependent on the number of years in which the influenza B lineage in the TIV matches the circulating B lineages. Assuming a moderate level of B cross-strain protection, TIV may be as effective as QIV. The choice of vaccination prioritisation has a greater impact than the QIV/TIV choice, with strategies targeting those most responsible for transmission being most effective.
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http://dx.doi.org/10.1111/irv.12367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910176PMC
July 2016

Parainfluenza Virus Infection Among Human Immunodeficiency Virus (HIV)-Infected and HIV-Uninfected Children and Adults Hospitalized for Severe Acute Respiratory Illness in South Africa, 2009-2014.

Open Forum Infect Dis 2015 Dec 19;2(4):ofv139. Epub 2015 Sep 19.

Center for Respiratory Diseases and Meningitis , National Institute for Communicable Diseases , Johannesburg ; School of Public Health.

Background.  Parainfluenza virus (PIV) is a common cause of acute respiratory tract infections, but little is known about PIV infection in children and adults in Africa, especially in settings where human immunodeficiency virus (HIV) prevalence is high. Methods.  We conducted active, prospective sentinel surveillance for children and adults hospitalized with severe acute respiratory illness (SARI) from 2009 to 2014 in South Africa. We enrolled controls (outpatients without febrile or respiratory illness) to calculate the attributable fraction for PIV infection. Respiratory specimens were tested by multiplex real-time reverse-transcription polymerase chain reaction assay for parainfluenza types 1, 2, and 3. Results.  Of 18 282 SARI cases enrolled, 1188 (6.5%) tested positive for any PIV type: 230 (19.4%) were type 1; 168 (14.1%) were type 2; 762 (64.1%) were type 3; and 28 (2.4%) had coinfection with 2 PIV types. After adjusting for age, HIV serostatus, and respiratory viral coinfection, the attributable fraction for PIV was 65.6% (95% CI [confidence interval], 47.1-77.7); PIV contributed to SARI among HIV-infected and -uninfected children <5 years of age and among individuals infected with PIV types 1 and 3. The observed overall incidence of PIV-associated SARI was 38 (95% CI, 36-39) cases per 100 000 population and was highest in children <1 year of age (925 [95% CI, 864-989] cases per 100 000 population). Compared with persons without HIV, persons with HIV had an increased relative risk of PIV hospitalization (9.4; 95% CI, 8.5-10.3). Conclusions.  Parainfluenza virus causes substantial severe respiratory disease in South Africa among children <5 years of age, especially those that are infected with HIV.
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http://dx.doi.org/10.1093/ofid/ofv139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630450PMC
December 2015

Assessing the impact of pneumococcal conjugate vaccines on invasive pneumococcal disease using polymerase chain reaction-based surveillance: an experience from South Africa.

BMC Infect Dis 2015 Oct 26;15:450. Epub 2015 Oct 26.

Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.

Background: The use of molecular diagnostic techniques for the evaluation of the impact of pneumococcal conjugate vaccines (PCVs) has not been documented. We aimed to evaluate the impact of PCVs on invasive pneumococcal disease (IPD) using polymerase chain reaction (PCR)-based techniques and compare with results obtained from culture-based methods.

Methods: We implemented two independent surveillance programs for IPD among individuals hospitalized at one large surveillance site in Soweto, South Africa during 2009-2012: (i) PCR-based (targeting the lytA gene) syndromic pneumonia surveillance; and (ii) culture-based laboratory surveillance. Positive samples were serotyped. The molecular serotyping assay included targets for 42 serotypes including all serotypes/serogroups included in the 7-valent (PCV-7) and 13-valent (PCV-13) PCV. The Quellung reaction was used for serotyping of culture-positive cases. We calculated the change in rates of IPD (lytA- or culture-positive) among HIV-uninfected children aged <2 years from the year of PCV-7 introduction (2009) to the post-vaccine years (2011 or 2012).

Results: During the study period there were 607 lytA-positive and 1,197 culture-positive cases that were serotyped. Samples with lytA cycle threshold (Ct)-values ≥35 (30.2 %; 123/407) were significantly less likely to have a serotype/serogroup detected for serotypes included in the molecular serotyping assay than those with Ct-values <35 (78.0 %; 156/200) (p < 0.001). From 2009 to 2012 rates of PCV-7 serotypes/serogroups decreased -63.8 % (95 % CI: -79.3 % to -39.1 %) among lytA-positive cases and -91.7 % (95 % CI: -98.8 % to -73.6 %) among culture-positive cases. Rates of lytA-positive non-vaccine serotypes/serogroups also significantly decreased (-71.7 %; 95 % CI: -81.1 % to -58.5 %) over the same period. Such decline was not observed among the culture-positive non-vaccine serotypes (1.2 %; 95 % CI: -96.7 % to 58.4 %).

Conclusions: Significant downward trends in IPD PCV-7 serotype-associated rates were observed among patients tested by PCR or culture methods; however trends of non-vaccine serotypes/serogroups differed between the two groups. Misclassifications of serotypes/serogroups, affecting the use of non-vaccine serotypes as a control group, may have occurred due to the low performance of the serotyping assay among lytA-positive cases with high Ct-values. Until PCR methods improve further, culture methods should continue to be used to monitor the effects of PCV vaccination programs on IPD incidence.
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http://dx.doi.org/10.1186/s12879-015-1198-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4620746PMC
October 2015