Human surveillance and phylogeny of highly pathogenic avian influenza A(H5N8) during an outbreak in poultry in South Africa, 2017.

BACKGROUND: In June 2017, an outbreak of the highly pathogenic avian influenza A(H5N8) was detected in commercial poultry farms in South Africa, which rapidly spread to all nine South African provinces. OBJECTIVES: We conducted active surveillance for the transmission of influenza A(H5N8) to humans working with infected birds during the South African outbreak. METHODS: Influenza A(H5N8)-positive veterinary specimens were used to evaluate the ability of real-time PCR-based assays to detect contemporary avian influenza A(H5N8) strains. Whole genome sequences were generated from these specimens by next-generation sequencing for phylogenetic characterization and screening for mammalian-adaptive mutations. RESULTS: Human respiratory samples from 74 individuals meeting our case definition, all tested negative for avian influenza A(H5) by real-time PCR, but 2 (3%) were positive for human influenza A(H3N2). 54% (40/74) reported wearing personal protective equipment including overalls, boots, gloves, masks, and goggles. 94% (59/63) of veterinary specimens positive for H5N8 were detected on an influenza A(H5) assay for human diagnostics. A commercial H5N8 assay detected H5 in only 6% (3/48) and N8 in 92% (44/48). Thirteen (13/25; 52%) A(H5N8) genomes generated from veterinary specimens clustered in a single monophyletic clade. These sequences contained the NS (P42S) and PB2 (L89V) mutations noted as markers of mammalian adaptation. CONCLUSIONS: Diagnostic assays were able to detect and characterize influenza A(H5N8) viruses, but poor performance is reported for a commercial assay. Absence of influenza A(H5N8) in humans with occupational exposure and no clear impression of molecular adaptation for mammalian infection suggest that this avian pathogen continues to be low-risk human pathogen.

Outbreak of influenza A in a boarding school in South Africa, 2016.

INTRODUCTION: We investigated an outbreak of influenza-like illness (ILI) at a boarding school in Eastern Cape Province, South Africa. We aimed to confirm the etiological agent, estimate attack rates and identify risk factors for illness. METHODS: We conducted a retrospective cohort study including senior school boarders (n=308). Students with ILI (cough and fever) were identified through school medical records. We also conducted a questionnaire-based cross-sectional study among senior students including boarders (n=107) and day students (n=45). We collected respiratory specimens for respiratory pathogen testing by real-time polymerase chain reaction from a subset of symptomatic students. We calculated attack rates of medically attended ILI (medILI) and identified factors associated with medILI using logistic regression. We calculated seasonal influenza vaccine effectiveness (VE) against medILI. RESULTS: Influenza A (H3N2) virus was detected in 61% (23/38) of specimens. Attack rate for medILI was 13% among boarders (39/308) in the cohort study and 20% in both day students (9/45) and boarders (21/107) in the cross-sectional study. Playing squash was associated with medILI (aOR 5.35, 95% confidence interval [95% CI]: 1.68-17.07). Of the boarders, 19% (57/308) were vaccinated before the outbreak. The adjusted VE against medILI was 18% (aOR 0.82, 95% CI 0.38-1.78). The outbreak led to cancellation of several events and the need for academic remedial sessions. CONCLUSION: We confirmed an influenza A (H3N2) virus outbreak with a high attack rate. The outbreak affected academic and sports activities. Participation in sports and social gatherings while experiencing ILI should be discouraged to reduce viral transmission and impact on school activities.

Replacement of neuraminidase inhibitor-susceptible influenza A(H1N1) with resistant phenotype in 2008 and circulation of susceptible influenza A and B viruses during 2009-2013, South Africa.

BACKGROUND: Data on the susceptibility of influenza viruses from South Africa to neuraminidase inhibitors (NAIs) are scarce, and no extensive analysis was done. OBJECTIVES: We aimed to determine oseltamivir and zanamivir susceptibility of influenza A and B virus neuraminidases (NAs), 2007-2013, South Africa. PATIENTS/METHODS: We enrolled participants through national influenza-like illness surveillance, 2007-2013. Influenza diagnosis was by virus isolation and quantitative polymerase chain reaction (qPCR). Drug susceptibility was determined by chemiluminescence-based NA-STAR/NA-XTD assay. Sanger sequencing was used to determine molecular markers of NAI resistance. RESULTS: Forty percent (6341/15 985) of participants were positive for influenza viruses using virus isolation (2007-2009) and qPCR (2009-2013) methods. A total of 1236/6341 (19.5%) virus isolates were generated of which 307/1236 (25%) were tested for drug susceptibility. During 2007-2008, the median 50% inhibitory concentration (IC50 ) of oseltamivir for seasonal influenza A(H1N1) increased from of 0.08 nmol/L (range 0.01-3.60) in 2007 to 73 nmol/L (range 1.56-305 nmol/L) in 2008. Influenza A isolates from 2009 to 2013 were susceptible to oseltamivir [A(H3N2) median IC50  = 0.05 nmol/L (range 0.01-0.08); A(H1N1)pdm09 = 0.11 nmol/L (range 0.01-0.78)] and zanamivir [A(H3N2) median IC50  = 0.56 nmol/L (range 0.47-0.66); A(H1N1)pdm09 = 0.35 nmol/L (range 0.27-0.533)]. Influenza B viruses were susceptible to both NAIs. NAI resistance-associated substitutions H275Y, E119V, and R150K (N1 numbering) were not detected in influenza A viruses that circulated in 2009-2013. CONCLUSIONS: We confirm replacement of NAI susceptible by resistant phenotype influenza A(H1N1) in 2008. Influenza A and B viruses (2009-2013) remained susceptible to NAIs; therefore, these drugs are useful for treating influenza-infected patients.

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

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

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

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

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

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