An evaluation of an influenza vaccination campaign targeting pregnant women in 27 clinics in two provinces of South Africa, 2015 - 2018.

INTRODUCTION: Despite prioritization, routine antenatal influenza vaccine coverage is < 16% in South Africa. We aimed to describe maternal influenza vaccine coverage in 27 antenatal clinics (ANCs) in Gauteng and Western Cape (WC) Provinces, where in collaboration with the Department of Health (DoH), we augmented the annual influenza vaccination programme among pregnant women. METHODS: From 2015 through 2018, 40,230 additional doses of influenza vaccine were added to the available stock and administered as part of routine antenatal care. Educational talks were given daily and data were collected on women attending ANCs. We compared characteristics of vaccinated and unvaccinated women using multivariable logistic regression. RESULTS: We screened 62,979 pregnant women during the period when Southern Hemisphere influenza vaccines were available (27,068 in Gauteng and 35,911 in WC). Vaccine coverage at the targeted clinics was 78.7% (49,355/62682), although pregnant women in WC were more likely to be vaccinated compared to those in the Gauteng (Odds ratio (OR) =3.7 p < 0.001). Women aged 25-29 and > 35 years were less likely to be vaccinated than women aged 18-24 years (OR = 0.9 p = 0.053; OR = 0.9 p < 0.001). HIV positive status was not associated with vaccination (OR = 1.0 p = 0.266). Reasons for not vaccinating included: vaccine stock-outs where ANCs depleted available stock of vaccines and/or were awaiting delivery of vaccines (54.6%, 6949/12723), refusal/indecision (25.8%, 3285), and current illness that contraindicated vaccination (19.6%, 2489). CONCLUSION: Antenatal vaccination uptake was likely improved by the increased vaccine supply and vaccine education offered during our campaign.

Decline of influenza and respiratory syncytial virus detection in facility-based surveillance during the COVID-19 pandemic, South Africa, January to October 2020.

BackgroundIn South Africa, COVID-19 control measures to prevent SARS-CoV-2 spread were initiated on 16 March 2020. Such measures may also impact the spread of other pathogens, including influenza virus and respiratory syncytial virus (RSV) with implications for future annual epidemics and expectations for the subsequent northern hemisphere winter.MethodsWe assessed the detection of influenza and RSV through facility-based syndromic surveillance of adults and children with mild or severe respiratory illness in South Africa from January to October 2020, and compared this with surveillance data from 2013 to 2019.ResultsFacility-based surveillance revealed a decline in influenza virus detection during the regular season compared with previous years. This was observed throughout the implementation of COVID-19 control measures. RSV detection decreased soon after the most stringent COVID-19 control measures commenced; however, an increase in RSV detection was observed after the typical season, following the re-opening of schools and the easing of measures.ConclusionCOVID-19 non-pharmaceutical interventions led to reduced circulation of influenza and RSV in South Africa. This has limited the country's ability to provide influenza virus strains for the selection of the annual influenza vaccine. Delayed increases in RSV case numbers may reflect the easing of COVID-19 control measures. An increase in influenza virus detection was not observed, suggesting that the measures may have impacted the two pathogens differently. The impact that lowered and/or delayed influenza and RSV circulation in 2020 will have on the intensity and severity of subsequent annual epidemics is unknown and warrants close monitoring.

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

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.

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

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.

Heterogeneity in influenza seasonality and vaccine effectiveness in Australia, Chile, New Zealand and South Africa: early estimates of the 2019 influenza season.

We compared 2019 influenza seasonality and vaccine effectiveness (VE) in four southern hemisphere countries: Australia, Chile, New Zealand and South Africa. Influenza seasons differed in timing, duration, intensity and predominant circulating viruses. VE estimates were also heterogeneous, with all-ages point estimates ranging from 7-70% (I2: 33%) for A(H1N1)pdm09, 4-57% (I2: 49%) for A(H3N2) and 29-66% (I2: 0%) for B. Caution should be applied when attempting to use southern hemisphere data to predict the northern hemisphere influenza season.

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

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.

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

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.

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

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.

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

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.

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.

In- and Out-of-hospital Mortality Associated with Seasonal and Pandemic Influenza and Respiratory Syncytial Virus in South Africa, 2009-2013.

Background: Estimates of influenza- and respiratory syncytial virus (RSV)-associated mortality burden are important to guide policy for control. Data are limited on the contribution of out-of-hospital deaths to this mortality. Methods: We modeled excess mortality attributable to influenza and RSV infection by applying regression models to weekly deaths from national vital statistics from 2009 through 2013, using influenza and RSV laboratory surveillance data as covariates. We fitted separate models for in- and out-of-hospital deaths. Results: There were 509791 average annual deaths in South Africa, of which 44% (95% confidence interval [CI] 43%-45%) occurred out-of-hospital. Seasonal influenza and RSV all-cause mortality rates were 23.0 (95% CI 11.0-30.6) and 13.2 (95% CI 6.4-33.8) per 100000 population annually (2.3% [95%CI 2.3%-2.4%] and 1.3% [95% CI 1.2%-1.4%] of all deaths respectively). The peak mortality rate was in individuals aged ≥75 years (386.0; 95% CI 176.5-466.3) for influenza and in infants (143.4; 95% CI 0-194.8) for RSV. Overall, 63% (95% CI 62%--65%) of seasonal influenza and 48% (95% CI 47%-49%) of RSV-associated deaths occurred out-of-hospital. Among children aged <5 years, RSV-associated deaths were more likely to occur in-hospital, whereas influenza-associated deaths were more likely to occur out-of-hospital. The mortality rate was 6.7 (95% CI 6.4-33.8) in the first influenza A(H1N1)pdm09 wave in 2009 and 20.9 (95% CI 6.4-33.8) in the second wave in 2011, with 30% (95% CI 29%-32%) of A(H1N1)pdm09-associated deaths in 2009 occurring out-of-hospital. Discussion: More than 45% of seasonal influenza- and RSV-associated deaths occur out-of-hospital in South Africa. These data suggest that hospital-based studies may substantially underestimate mortality burden.

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

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.

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.

Effectiveness of seasonal influenza vaccination in community-dwelling elderly people: an individual participant data meta-analysis of test-negative design case-control studies.

BACKGROUND: Several aggregate data meta-analyses have provided estimates of the effectiveness of influenza vaccination in community-dwelling elderly people. However, these studies ignored the effects of patient-level confounders such as sex, age, and chronic diseases that could bias effectiveness estimates. We aimed to assess the confounder-adjusted effectiveness of influenza vaccines on laboratory-confirmed influenza among elderly people by conducting a global individual participant data meta-analysis. METHODS: In this individual participant data meta-analysis, we considered studies included in a previously conducted aggregate data meta-analysis that included test-negative design case-control studies published up to July 13, 2014. We contacted all authors of the included studies on Dec 1, 2014, to request individual participant data. Patients were excluded if their unique identifier was missing, their vaccination status was unknown, their outcome status was unknown, or they had had suspected influenza infection more than once in the same influenza season. Cases were patients with influenza-like illness symptoms who tested positive for at least one of A H1N1, A H1N1 pdm09, A H3N2, or B viruses; controls were patients with influenza-like illness symptoms who tested negative for these virus types or subtypes. Influenza vaccine effectiveness against overall and subtype-specific laboratory-confirmed influenza were the primary and secondary outcomes. We used a generalised linear mixed model to calculate adjusted vaccine effectiveness according to vaccine match to the circulating strains of influenza virus and intensity of the virus activity (epidemic or non-epidemic). Vaccine effectiveness was defined as the relative reduction in risk of laboratory-confirmed influenza in vaccinated patients compared with unvaccinated patients. We did subgroup analyses to estimate vaccine effectiveness according to hemisphere, age category, and health status. FINDINGS: We received 23 of the 53 datasets included in the aggregate data meta-analysis. Furthermore, six additional datasets were provided by data collaborators, which resulted in individual participant data for a total of 5210 participants. A total of 4975 patients had the required data for analysis. Of these, 3146 (63%) were controls and 1829 (37%) were cases. Influenza vaccination was significantly effective during epidemic seasons irrespective of vaccine match status (matched adjusted vaccine effectiveness 44·38%, 95% CI 22·63-60·01; mismatched adjusted vaccine effectiveness 20·00%, 95% CI 3·46-33·68; analyses in the imputed dataset). Seasonal influenza vaccination did not show significant effectiveness during non-epidemic seasons. We found substantial variation in vaccine effectiveness across virus types and subtypes, with the highest estimate for A H1N1 pdm09 (53·19%, 10·25-75·58) and the lowest estimate for B virus types (-1·52%, -39·58 to 26·16). Although we observed no significant differences between subgroups in each category (hemisphere, age, and health status), influenza vaccination showed a protective effect among elderly people with cardiovascular disease, lung disease, or aged 75 years and younger. INTERPRETATION: Influenza vaccination is moderately effective against laboratory-confirmed influenza in elderly people during epidemic seasons. More research is needed to investigate factors affecting vaccine protection (eg, brand-specific or type-specific vaccine effectiveness and repeated annual vaccination) in elderly people. FUNDING: University Medical Center Groningen.

Estimating vaccine effectiveness in preventing laboratory-confirmed influenza in outpatient settings in South Africa, 2015.

Trivalent seasonal influenza vaccine effectiveness during the 2015 season in South Africa was assessed using a test-negative case control study design. Influenza A(H1N1)pdm09 was the dominant circulating strain. Overall influenza vaccine coverage was 3.2% (29/899). The vaccine effectiveness estimate, against any influenza virus infection, adjusted for age, underlying conditions and timing within season was 46.2% (95% CI: -23.5 to 76.5), and 53.6% (95% CI: -62.6 to 80.3) against influenza A(H1N1)pdm09.

Mortality Associated With Seasonal and Pandemic Influenza Among Pregnant and Nonpregnant Women of Childbearing Age in a High-HIV-Prevalence Setting-South Africa, 1999-2009.

BACKGROUND: Information on the mortality burden associated with seasonal and pandemic influenza virus infection among pregnant women is scarce in most settings, particularly in sub-Saharan Africa where pregnancy and maternal mortality rates as well as human immunodeficiency virus (HIV) prevalence are elevated. METHODS: We used an ecological study design to estimate the seasonal and A(H1N1)pdm09 influenza-associated mortality among pregnant and nonpregnant women of childbearing age (15-49 years) by HIV serostatus during 1999-2009 in South Africa. Mortality rates were expressed per 100 000 person-years. RESULTS: During 1999-2009, the estimated mean annual seasonal influenza-associated mortality rates were 12.6 (123 deaths) and 7.3 (914 deaths) among pregnant and nonpregnant women, respectively. Among pregnant women, the estimated mean annual seasonal influenza-associated mortality rates were 74.9 (109 deaths) among HIV-infected and 1.5 (14 deaths) among HIV-uninfected individuals. Among nonpregnant women, the estimated mean annual seasonal influenza-associated mortality rate was 41.2 (824 deaths) among HIV-infected and 0.9 (90 deaths) among HIV-uninfected individuals. Pregnant women experienced an increased risk of seasonal influenza-associated mortality compared with nonpregnant women (relative risk [RR], 2.8; 95% confidence interval [CI], 1.7-3.9). In 2009, the estimated influenza A(H1N1)pdm09-associated mortality rates were 19.3 (181 deaths) and 9.4 (1189 deaths) among pregnant and nonpregnant women, respectively (RR, 3.2; 95% CI, 2.3-4.1). CONCLUSIONS: Among women of childbearing age, the majority of estimated seasonal influenza-associated deaths occurred in HIV-infected individuals. Pregnant women experienced an increased risk of death associated with seasonal and A(H1N1)pdm09 influenza infection compared with nonpregnant women.

Evaluation of influenza vaccine effectiveness and description of circulating strains in outpatient settings in South Africa, 2014.

The effectiveness of the trivalent seasonal influenza vaccine during the 2014 season in South Africa was assessed using a test-negative case-control study design including 472 cases and 362 controls. Influenza A(H3N2) was the dominant strain circulating. The overall vaccine effectiveness estimate, adjusted for age and underlying conditions, was 43·1% (95% CI: -26·8-74·5). 2014 H3N2 viruses from South Africa were mainly in sublineage 3C.3 with accumulation of amino acid changes that differentiate them from the vaccine strain in 3C.1.

Deaths associated with respiratory syncytial and influenza viruses among persons ≥5 years of age in HIV-prevalent area, South Africa, 1998-2009(1).

We estimated deaths attributable to influenza and respiratory syncytial virus (RSV) among persons >5 years of age in South Africa during 1998-2009 by applying regression models to monthly deaths and laboratory surveillance data. Rates were expressed per 100,000 person-years. The mean annual number of seasonal influenza-associated deaths was 9,093 (rate 21.6). Persons >65 years of age and HIV-positive persons accounted for 50% (n = 4,552) and 28% (n = 2,564) of overall seasonal influenza-associated deaths, respectively. In 2009, we estimated 4,113 (rate 9.2) influenza A(H1N1)pdm09-associated deaths. The mean of annual RSV-associated deaths during the study period was 511 (rate 1.2); no RSV-associated deaths were estimated in persons >45 years of age. Our findings support the recommendation for influenza vaccination of older persons and HIV-positive persons. Surveillance for RSV should be strengthened to clarify the public health implications and severity of illness associated with RSV infection in South Africa.

Effectiveness and knowledge, attitudes and practices of seasonal influenza vaccine in primary healthcare settings in South Africa, 2010-2013.

OBJECTIVES: Influenza vaccine effectiveness (VE) and coverage data for sub-Saharan Africa are scarce. Using a test-negative case-control design, we estimated influenza VE annually among individuals with influenza-like illness presenting to an outpatient sentinel surveillance programme in South Africa from 2010 to 2013. A knowledge, attitudes and practices (KAP) influenza vaccine survey of programme clinicians was conducted in 2013. SAMPLE: In total, 9420 patients were enrolled in surveillance of whom 5344 (56.7%) were included in the VE analysis: 2678 (50.1%) were classified as controls (influenza test-negative) and 2666 (49.9%) as cases (influenza test-positive). RESULTS: Mean annual influenza vaccine coverage among controls was 4.5% for the four years. Annual VE estimates adjusted for age, underlying medical conditions and seasonality for 2010-2013 were 54.2% (95% confidence interval (CI): 2.4-78.6%), 57.1% (95% CI: 15.5-78.2%), 38.4% (95% CI: -71.7-78.1%) and 87.2% (95% CI: 67.2-95.0%), respectively. The KAP survey showed that >90% of clinicians were familiar with the indications for and the benefits of influenza vaccination. CONCLUSIONS: Our study showed that the vaccine was significantly protective in 2010, 2011 and 2013, but not in 2012 when the circulating A(H3N2) strain showed genetic drift. Vaccine coverage was low despite good clinician knowledge of vaccination indications. Further studies are needed to investigate the reason for the low uptake of influenza vaccine.