Publications by authors named "Cheryl Cohen"

172 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

SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma.

Nat Med 2021 Mar 2. Epub 2021 Mar 2.

National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service (NHLS), Johannesburg, South Africa.

SARS-CoV-2 501Y.V2 (B.1.351), a novel lineage of coronavirus causing COVID-19, contains substitutions in two immunodominant domains of the spike protein. Here, we show that pseudovirus expressing 501Y.V2 spike protein completely escapes three classes of therapeutically relevant antibodies. This pseudovirus also exhibits substantial to complete escape from neutralization, but not binding, by convalescent plasma. These data highlight the prospect of reinfection with antigenically distinct variants and foreshadows reduced efficacy of spike-based vaccines.
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http://dx.doi.org/10.1038/s41591-021-01285-xDOI Listing
March 2021

Global burden of influenza-associated lower respiratory tract infections and hospitalizations among adults: A systematic review and meta-analysis.

PLoS Med 2021 Mar 1;18(3):e1003550. Epub 2021 Mar 1.

Division of Global Health Protection, US Centers for Disease Control and Prevention, Nairobi, Kenya.

Background: Influenza illness burden is substantial, particularly among young children, older adults, and those with underlying conditions. Initiatives are underway to develop better global estimates for influenza-associated hospitalizations and deaths. Knowledge gaps remain regarding the role of influenza viruses in severe respiratory disease and hospitalizations among adults, particularly in lower-income settings.

Methods And Findings: We aggregated published data from a systematic review and unpublished data from surveillance platforms to generate global meta-analytic estimates for the proportion of acute respiratory hospitalizations associated with influenza viruses among adults. We searched 9 online databases (Medline, Embase, CINAHL, Cochrane Library, Scopus, Global Health, LILACS, WHOLIS, and CNKI; 1 January 1996-31 December 2016) to identify observational studies of influenza-associated hospitalizations in adults, and assessed eligible papers for bias using a simplified Newcastle-Ottawa scale for observational data. We applied meta-analytic proportions to global estimates of lower respiratory infections (LRIs) and hospitalizations from the Global Burden of Disease study in adults ≥20 years and by age groups (20-64 years and ≥65 years) to obtain the number of influenza-associated LRI episodes and hospitalizations for 2016. Data from 63 sources showed that influenza was associated with 14.1% (95% CI 12.1%-16.5%) of acute respiratory hospitalizations among all adults, with no significant differences by age group. The 63 data sources represent published observational studies (n = 28) and unpublished surveillance data (n = 35), from all World Health Organization regions (Africa, n = 8; Americas, n = 11; Eastern Mediterranean, n = 7; Europe, n = 8; Southeast Asia, n = 11; Western Pacific, n = 18). Data quality for published data sources was predominantly moderate or high (75%, n = 56/75). We estimate 32,126,000 (95% CI 20,484,000-46,129,000) influenza-associated LRI episodes and 5,678,000 (95% CI 3,205,000-9,432,000) LRI hospitalizations occur each year among adults. While adults <65 years contribute most influenza-associated LRI hospitalizations and episodes (3,464,000 [95% CI 1,885,000-5,978,000] LRI hospitalizations and 31,087,000 [95% CI 19,987,000-44,444,000] LRI episodes), hospitalization rates were highest in those ≥65 years (437/100,000 person-years [95% CI 265-612/100,000 person-years]). For this analysis, published articles were limited in their inclusion of stratified testing data by year and age group. Lack of information regarding influenza vaccination of the study population was also a limitation across both types of data sources.

Conclusions: In this meta-analysis, we estimated that influenza viruses are associated with over 5 million hospitalizations worldwide per year. Inclusion of both published and unpublished findings allowed for increased power to generate stratified estimates, and improved representation from lower-income countries. Together, the available data demonstrate the importance of influenza viruses as a cause of severe disease and hospitalizations in younger and older adults worldwide.
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http://dx.doi.org/10.1371/journal.pmed.1003550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959367PMC
March 2021

Estimated impact of the pneumococcal conjugate vaccine on pneumonia mortality in South Africa, 1999 through 2016: An ecological modelling study.

PLoS Med 2021 Feb 16;18(2):e1003537. Epub 2021 Feb 16.

Centre for Respiratory Diseases and Meningitis (CRDM), National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service (NHLS), Johannesburg, South Africa.

Background: Data on the national-level impact of pneumococcal conjugate vaccine (PCV) introduction on mortality are lacking from Africa. PCV was introduced in South Africa in 2009. We estimated the impact of PCV introduction on all-cause pneumonia mortality in South Africa, while controlling for changes in mortality due to other interventions.

Methods And Findings: We used national death registration data in South Africa from 1999 to 2016 to assess the impact of PCV introduction on all-cause pneumonia mortality in all ages, with the exclusion of infants aged <1 month. We created a composite (synthetic) control using Bayesian variable selection of nondiarrheal, nonpneumonia, and nonpneumococcal deaths to estimate the number of expected all-cause pneumonia deaths in the absence of PCV introduction post 2009. We compared all-cause pneumonia deaths from the death registry to the expected deaths in 2012 to 2016. We also estimated the number of prevented deaths during 2009 to 2016. Of the 9,324,638 deaths reported in South Africa from 1999 to 2016, 12·6% were pneumonia-related. Compared to number of deaths expected, we estimated a 33% (95% credible interval (CrI) 26% to 43%), 23% (95%CrI 17% to 29%), 25% (95%CrI 19% to 32%), and 23% (95%CrI 11% to 32%) reduction in pneumonia mortality in children aged 1 to 11 months, 1 to 4 years, 5 to 7 years, and 8 to 18 years in 2012 to 2016, respectively. In total, an estimated 18,422 (95%CrI 12,388 to 26,978) pneumonia-related deaths were prevented from 2009 to 2016 in children aged <19 years. No declines were estimated observed among adults following PCV introduction. This study was mainly limited by coding errors in original data that could have led to a lower impact estimate, and unmeasured factors could also have confounded estimates.

Conclusions: This study found that the introduction of PCV was associated with substantial reduction in all-cause pneumonia deaths in children aged 1 month to <19 years. The model predicted an effect of PCV in age groups who were eligible for vaccination (1 months to 4 years), and an indirect effect in those too old (8 to 18 years) to be vaccinated. These findings support sustaining pneumococcal vaccination to reduce pneumonia-related mortality in children.
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http://dx.doi.org/10.1371/journal.pmed.1003537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924778PMC
February 2021

Epidemiology of pertussis in individuals of all ages hospitalised with respiratory illness in South Africa, January 2013 - December 2018.

Clin Infect Dis 2021 Feb 2. Epub 2021 Feb 2.

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

Background: Policy recommendations on pertussis vaccination need to be guided by data, which are limited from low- and middle-income countries. We aimed to describe the epidemiology of pertussis in South Africa, a country with high HIV prevalence and routine pertussis vaccination for six decades including the acellular vaccine since 2009.

Methods: Hospitalized patients of all ages were enrolled at five sentinel sites as part of a pneumonia surveillance program from January 2013 through December 2018. Nasopharyngeal specimens and induced sputum were tested by PCR for Bordetella pertussis. In addition, demographic and clinical information were collected. Incidence rates were calculated for 2013-2016, and multivariable logistic regression performed to identify factors associated with pertussis.

Results: Over the six-year period 19429 individuals were enrolled, of which 239 (1.2%) tested positive for B. pertussis. Detection rate was highest in infants aged <6 months (2.8%, 155/5524). Mean annual incidence was 17 cases per 100,000 population, with the highest incidence in children <1 year of age (228 per 100,000). Age-adjusted incidence was 65.9 per 100,000 in HIV-infected individuals compared to 8.5 per 100,000 in HIV-uninfected individuals (risk ratio 30.4, 95% confidence interval 23.0-40.2). Ten individuals (4.2%) with pertussis died; of which 7 were infants aged <6 months and 3 were immunocompromised adults.

Conclusions: Pertussis continues to be a significant cause of illness and hospitalization in South Africa, despite routine vaccination. The highest burden of disease and death occurred in infants; however, HIV-infected adults were also identified as an important group at risk of B. pertussis infection.
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http://dx.doi.org/10.1093/cid/ciab089DOI Listing
February 2021

SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma.

bioRxiv 2021 Jan 19. Epub 2021 Jan 19.

National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service (NHLS), Johannesburg, South Africa.

SARS-CoV-2 501Y.V2, a novel lineage of the coronavirus causing COVID-19, contains multiple mutations within two immunodominant domains of the spike protein. Here we show that this lineage exhibits complete escape from three classes of therapeutically relevant monoclonal antibodies. Furthermore 501Y.V2 shows substantial or complete escape from neutralizing antibodies in COVID-19 convalescent plasma. These data highlight the prospect of reinfection with antigenically distinct variants and may foreshadow reduced efficacy of current spike-based vaccines.
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http://dx.doi.org/10.1101/2021.01.18.427166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836116PMC
January 2021

A Retrospective observational cohort study of the effect of antenatal influenza vaccination on birth outcomes in Cape Town, South Africa, 2015-2016.

Influenza Other Respir Viruses 2021 Jan 16. Epub 2021 Jan 16.

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

Background: There are conflicting data concerning the impact of antenatal influenza vaccination on birth outcomes including low birthweight (LBW), preterm birth, small for gestational age (SGA), and stillbirth.

Methods: We conducted a retrospective observational cohort study of infants born to women residing in Mitchells Plain, Cape Town. Infants were born at 4 health facilities during May 28 - December 31, 2015 and April 15 - December 31, 2016. We performed crude and multivariable logistic regression, propensity score (PS) matching logistic regression, and inverse probability of treatment weighted (IPTW) regression to assess vaccine effectiveness (VE) against LBW, preterm birth, SGA, and stillbirth adjusting for measured confounders.

Results: Maternal vaccination status, antenatal history, and ≥1 birth outcome(s) were available for 4084/5333 (76.6%) pregnancies, 2109 (51.6%) vaccinated, and 1975 (48.4%) unvaccinated. The proportion LBW was lower in vaccinated (6.9%) vs. unvaccinated (12.5%) in multivariable [VE 0.27 (95% CI 0.07-0.42)], PS [VE 0.30 (95% CI 0.09-0.51)], and IPTW [VE 0.24 (95% CI 0.04-0.45)]. Preterm birth was less frequent in vaccinated (8.6%) than unvaccinated (16.4%) in multivariable [VE 0.26 (0.09-0.40)], PS [VE 0.25 (95% CI 0.09-0.41)], and IPTW [VE 0.34 (95% CI 0.18-0.51)]. The proportion SGA was lower in vaccinated (6.0%) than unvaccinated (8.8%) but not in adjusted models. There were few stillbirths in our study population, 30/4084 (0.7%).

Conclusions: Using multiple analytic approaches, we found that influenza vaccination was associated with lower prevalence of LBW (24-30%) and preterm birth (25-34%) in Cape Town during 2015-2016.
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http://dx.doi.org/10.1111/irv.12836DOI Listing
January 2021

A cost-effectiveness analysis of South Africa's seasonal influenza vaccination programme.

Vaccine 2021 01 1;39(2):412-422. Epub 2020 Dec 1.

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.

Background: Seasonal influenza imposes a significant health and economic burden in South Africa, particularly in populations vulnerable to severe consequences of influenza. This study assesses the cost-effectiveness of South Africa's seasonal influenza vaccination strategy, which involves vaccinating vulnerable populations with trivalent inactivated influenza vaccine (TIV) during routine facility visits. Vulnerable populations included in our analysis are persons aged ≥ 65 years; pregnant women; persons living with HIV/AIDS (PLWHA), persons of any age with underlying medical conditions (UMC) and children aged 6-59 months.

Method: We employed the World Health Organisation's (WHO) Cost Effectiveness Tool for Seasonal Influenza Vaccination (CETSIV), a decision tree model, to evaluate the 2018 seasonal influenza vaccination campaign from a public healthcare provider and societal perspective. CETSIV was populated with existing country-specific demographic, epidemiologic and coverage data to estimate incremental cost-effectiveness ratios (ICERs) by comparing costs and benefits of the influenza vaccination programme to no vaccination.

Results: The highest number of clinical events (influenza cases, outpatient visits, hospitalisation and deaths) were averted in PLWHA and persons with other UMCs. Using a cost-effectiveness threshold of US$ 3400 per quality-adjusted life year (QALY), our findings suggest that the vaccination programme is cost-effective for all vulnerable populations except for children aged 6-59 months. ICERs ranged from ~US$ 1 750 /QALY in PLWHA to ~US$ 7500/QALY in children. In probabilistic sensitivity analyses, the vaccination programme was cost-effective in pregnant women, PLWHA, persons with UMCs and persons aged ≥65 years in >80% of simulations. These findings were robust to changes in many model inputs but were most sensitive to uncertainty in estimates of influenza-associated illness burden.

Conclusion: South Africa's seasonal influenza vaccination strategy of opportunistically targeting vulnerable populations during routine visits is cost-effective. A budget impact analysis will be useful for supporting future expansions of the programme.
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http://dx.doi.org/10.1016/j.vaccine.2020.11.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804372PMC
January 2021

Global burden of acute lower respiratory infection associated with human metapneumovirus in children under 5 years in 2018: a systematic review and modelling study.

Lancet Glob Health 2021 01 26;9(1):e33-e43. Epub 2020 Nov 26.

Centre for Global Health, Usher Institute, Edinburgh Medical School, University of Edinburgh, Edinburgh, UK. Electronic address:

Background: Human metapneumovirus is a common virus associated with acute lower respiratory infections (ALRIs) in children. No global burden estimates are available for ALRIs associated with human metapneumovirus in children, and no licensed vaccines or drugs exist for human metapneumovirus infections. We aimed to estimate the age-stratified human metapneumovirus-associated ALRI global incidence, hospital admissions, and mortality burden in children younger than 5 years.

Methods: We estimated the global burden of human metapneumovirus-associated ALRIs in children younger than 5 years from a systematic review of 119 studies published between Jan 1, 2001, and Dec 31, 2019, and a further 40 high quality unpublished studies. We assessed risk of bias using a modified Newcastle-Ottawa Scale. We estimated incidence, hospital admission rates, and in-hospital case-fatality ratios (hCFRs) of human metapneumovirus-associated ALRI using a generalised linear mixed model. We applied incidence and hospital admission rates of human metapneumovirus-associated ALRI to population estimates to yield the morbidity burden estimates by age bands and World Bank income levels. We also estimated human metapneumovirus-associated ALRI in-hospital deaths and overall human metapneumovirus-associated ALRI deaths (both in-hospital and non-hospital deaths). Additionally, we estimated human metapneumovirus-attributable ALRI cases, hospital admissions, and deaths by combining human metapneumovirus-associated burden estimates and attributable fractions of human metapneumovirus in laboratory-confirmed human metapneumovirus cases and deaths.

Findings: In 2018, among children younger than 5 years globally, there were an estimated 14·2 million human metapneumovirus-associated ALRI cases (uncertainty range [UR] 10·2 million to 20·1 million), 643 000 human metapneumovirus-associated hospital admissions (UR 425 000 to 977 000), 7700 human metapneumovirus-associated in-hospital deaths (2600 to 48 800), and 16 100 overall (hospital and community) human metapneumovirus-associated ALRI deaths (5700 to 88 000). An estimated 11·1 million ALRI cases (UR 8·0 million to 15·7 million), 502 000 ALRI hospital admissions (UR 332 000 to 762 000), and 11 300 ALRI deaths (4000 to 61 600) could be causally attributed to human metapneumovirus in 2018. Around 58% of the hospital admissions were in infants under 12 months, and 64% of in-hospital deaths occurred in infants younger than 6 months, of which 79% occurred in low-income and lower-middle-income countries.

Interpretation: Infants younger than 1 year have disproportionately high risks of severe human metapneumovirus infections across all World Bank income regions and all child mortality settings, similar to respiratory syncytial virus and influenza virus. Infants younger than 6 months in low-income and lower-middle-income countries are at greater risk of death from human metapneumovirus-associated ALRI than older children and those in upper-middle-income and high-income countries. Our mortality estimates demonstrate the importance of intervention strategies for infants across all settings, and warrant continued efforts to improve the outcome of human metapneumovirus-associated ALRI among young infants in low-income and lower-middle-income countries.

Funding: Bill & Melinda Gates Foundation.
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http://dx.doi.org/10.1016/S2214-109X(20)30393-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783516PMC
January 2021

Influenza surveillance capacity improvements in Africa during 2011-2017.

Influenza Other Respir Viruses 2020 Nov 4. Epub 2020 Nov 4.

Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.

Background: Influenza surveillance helps time prevention and control interventions especially where complex seasonal patterns exist. We assessed influenza surveillance sustainability in Africa where influenza activity varies and external funds for surveillance have decreased.

Methods: We surveyed African Network for Influenza Surveillance and Epidemiology (ANISE) countries about 2011-2017 surveillance system characteristics. Data were summarized with descriptive statistics and analyzed with univariate and multivariable analyses to quantify sustained or expanded influenza surveillance capacity in Africa.

Results: Eighteen (75%) of 24 ANISE members participated in the survey; their cumulative population of 710 751 471 represent 56% of Africa's total population. All 18 countries scored a mean 95% on WHO laboratory quality assurance panels. The number of samples collected from severe acute respiratory infection case-patients remained consistent between 2011 and 2017 (13 823 vs 13 674 respectively) but decreased by 12% for influenza-like illness case-patients (16 210 vs 14 477). Nine (50%) gained capacity to lineage-type influenza B. The number of countries reporting each week to WHO FluNet increased from 15 (83%) in 2011 to 17 (94%) in 2017.

Conclusions: Despite declines in external surveillance funding, ANISE countries gained additional laboratory testing capacity and continued influenza testing and reporting to WHO. These gains represent important achievements toward sustainable surveillance and epidemic/pandemic preparedness.
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http://dx.doi.org/10.1111/irv.12818DOI Listing
November 2020

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

Decreased Influenza Activity During the COVID-19 Pandemic - United States, Australia, Chile, and South Africa, 2020.

MMWR Morb Mortal Wkly Rep 2020 Sep 18;69(37):1305-1309. Epub 2020 Sep 18.

After recognition of widespread community transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), by mid- to late February 2020, indicators of influenza activity began to decline in the Northern Hemisphere. These changes were attributed to both artifactual changes related to declines in routine health seeking for respiratory illness as well as real changes in influenza virus circulation because of widespread implementation of measures to mitigate transmission of SARS-CoV-2. Data from clinical laboratories in the United States indicated a 61% decrease in the number of specimens submitted (from a median of 49,696 per week during September 29, 2019-February 29, 2020, to 19,537 during March 1-May 16, 2020) and a 98% decrease in influenza activity as measured by percentage of submitted specimens testing positive (from a median of 19.34% to 0.33%). Interseasonal (i.e., summer) circulation of influenza in the United States (May 17-August 8, 2020) is currently at historical lows (median = 0.20% tests positive in 2020 versus 2.35% in 2019, 1.04% in 2018, and 2.36% in 2017). Influenza data reported to the World Health Organization's (WHO's) FluNet platform from three Southern Hemisphere countries that serve as robust sentinel sites for influenza from Oceania (Australia), South America (Chile), and Southern Africa (South Africa) showed very low influenza activity during June-August 2020, the months that constitute the typical Southern Hemisphere influenza season. In countries or jurisdictions where extensive community mitigation measures are maintained (e.g., face masks, social distancing, school closures, and teleworking), those locations might have little influenza circulation during the upcoming 2020-21 Northern Hemisphere influenza season. The use of community mitigation measures for the COVID-19 pandemic, plus influenza vaccination, are likely to be effective in reducing the incidence and impact of influenza, and some of these mitigation measures could have a role in preventing influenza in future seasons. However, given the novelty of the COVID-19 pandemic and the uncertainty of continued community mitigation measures, it is important to plan for seasonal influenza circulation in the United States this fall and winter. Influenza vaccination of all persons aged ≥6 months remains the best method for influenza prevention and is especially important this season when SARS-CoV-2 and influenza virus might cocirculate (1).
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http://dx.doi.org/10.15585/mmwr.mm6937a6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498167PMC
September 2020

Risk factors for COVID-19 death in a population cohort study from the Western Cape Province, South Africa.

Authors:
Andrew Boulle Mary-Ann Davies Hannah Hussey Muzzammil Ismail Erna Morden Ziyanda Vundle Virginia Zweigenthal Hassan Mahomed Masudah Paleker David Pienaar Yamanya Tembo Charlene Lawrence Washiefa Isaacs Hlengani Mathema Derick Allen Taryn Allie Jamy-Lee Bam Kasturi Buddiga Pierre Dane Alexa Heekes Boitumelo Matlapeng Themba Mutemaringa Luckmore Muzarabani Florence Phelanyane Rory Pienaar Catherine Rode Mariette Smith Nicki Tiffin Nesbert Zinyakatira Carol Cragg Frederick Marais Vanessa Mudaly Jacqueline Voget Jody Davids Francois Roodt Nellis van Zyl Smit Alda Vermeulen Kevin Adams Gordon Audley Kathleen Bateman Peter Beckwith Marc Bernon Dirk Blom Linda Boloko Jean Botha Adam Boutall Sean Burmeister Lydia Cairncross Gregory Calligaro Cecilia Coccia Chadwin Corin Remy Daroowala Joel A Dave Elsa De Bruyn Martin De Villiers Mimi Deetlefs Sipho Dlamini Thomas Du Toit Wilhelm Endres Tarin Europa Graham Fieggan Anthony Figaji Petro Frankenfeld Elizabeth Gatley Phindile Gina Evashan Govender Rochelle Grobler Manqoba Vusumuzi Gule Christoff Hanekom Michael Held Alana Heynes Sabelo Hlatswayo Bridget Hodkinson Jeanette Holtzhausen Shakeel Hoosain Ashely Jacobs Miriam Kahn Thania Kahn Arvin Khamajeet Joubin Khan Riaasat Khan Alicia Khwitshana Lauren Knight Sharita Kooverjee Rene Krogscheepers Jean Jacque Kruger Suzanne Kuhn Kim Laubscher John Lazarus Jacque Le Roux Scott Lee Jones Dion Levin Gary Maartens Thina Majola Rodgers Manganyi David Marais Suzaan Marais Francois Maritz Deborah Maughan Simthandile Mazondwa Luyanda Mbanga Nomonde Mbatani Bulewa Mbena Graeme Meintjes Marc Mendelson Ernst Möller Allison Moore Babalwa Ndebele Marc Nortje Ntobeko Ntusi Funeka Nyengane Chima Ofoegbu Nectarios Papavarnavas Jonny Peter Henri Pickard Kent Pluke Peter J Raubenheimer Gordon Robertson Julius Rozmiarek A Sayed Matthias Scriba Hennie Sekhukhune Prasun Singh Elsabe Smith Vuyolwethu Soldati Cari Stek Robert van den Berg Le Roux van der Merwe Pieter Venter Barbra Vermooten Gerrit Viljoen Santhuri Viranna Jonno Vogel Nokubonga Vundla Sean Wasserman Eddy Zitha Vanessa Lomas-Marais Annie Lombard Katrin Stuve Werner Viljoen De Vries Basson Sue Le Roux Ethel Linden-Mars Lizanne Victor Mark Wates Elbe Zwanepoel Nabilah Ebrahim Sa'ad Lahri Ayanda Mnguni Thomas Crede Martin de Man Katya Evans Clint Hendrikse Jonathan Naude Moosa Parak Patrick Szymanski Candice Van Koningsbruggen Riezaah Abrahams Brian Allwood Christoffel Botha Matthys Henndrik Botha Alistair Broadhurst Dirkie Claasen Che Daniel Riyaadh Dawood Marie du Preez Nicolene Du Toit Kobie Erasmus Coenraad F N Koegelenberg Shiraaz Gabriel Susan Hugo Thabiet Jardine Clint Johannes Sumanth Karamchand Usha Lalla Eduard Langenegger Eize Louw Boitumelo Mashigo Nonte Mhlana Chizama Mnqwazi Ashley Moodley Desiree Moodley Saadiq Moolla Abdurasiet Mowlana Andre Nortje Elzanne Olivier Arifa Parker Chané Paulsen Hans Prozesky Jacques Rood Tholakele Sabela Neshaad Schrueder Nokwanda Sithole Sthembiso Sithole Jantjie J Taljaard Gideon Titus Tian Van Der Merwe Marije van Schalkwyk Luthando Vazi Abraham J Viljoen Mogamat Yazied Chothia Vanessa Naidoo Lee Alan Wallis Mumtaz Abbass Juanita Arendse Rizqa Armien Rochelle Bailey Muideen Bello Rachel Carelse Sheron Forgus Nosi Kalawe Saadiq Kariem Mariska Kotze Jonathan Lucas Juanita McClaughlin Kathleen Murie Leilah Najjaar Liesel Petersen James Porter Melanie Shaw Dusica Stapar Michelle Williams Linda Aldum Natacha Berkowitz Raakhee Girran Kevin Lee Lenny Naidoo Caroline Neumuller Kim Anderson Kerrin Begg Lisa Boerlage Morna Cornell Renée de Waal Lilian Dudley René English Jonathan Euvrard Pam Groenewald Nisha Jacob Heather Jaspan Emma Kalk Naomi Levitt Thoko Malaba Patience Nyakato Gabriela Patten Helen Schneider Maylene Shung King Priscilla Tsondai James Van Duuren Nienke van Schaik Lucille Blumberg Cheryl Cohen Nelesh Govender Waasila Jassat Tendesayi Kufa Kerrigan McCarthy Lynn Morris Nei-Yuan Hsiao Ruan Marais Jon Ambler Olina Ngwenya Richard Osei-Yeboah Leigh Johnson Reshma Kassanjee Tsaone Tamuhla

Clin Infect Dis 2020 Aug 29. Epub 2020 Aug 29.

Division of Computational Biology, University of Cape Town.

Background: Risk factors for COVID-19 death in sub-Saharan Africa and the effects of HIV and tuberculosis on COVID-19 outcomes are unknown.

Methods: We conducted a population cohort study using linked data from adults attending public sector health facilities in the Western Cape, South Africa. We used Cox-proportional hazards models adjusted for age, sex, location and comorbidities to examine the association between HIV, tuberculosis and COVID-19 death from 1 March-9 June 2020 among (i) public sector "active patients" (≥1 visit in the 3 years before March 2020), (ii) laboratory-diagnosed COVID-19 cases and (iii) hospitalized COVID-19 cases. We calculated the standardized mortality ratio (SMR) for COVID-19 comparing HIV positive vs. negative adults using modelled population estimates.

Results: Among 3,460,932 patients (16% HIV positive), 22,308 were diagnosed with COVID-19, of whom 625 died. COVID-19 death was associated with male sex, increasing age, diabetes, hypertension and chronic kidney disease. HIV was associated with COVID-19 mortality (adjusted hazard ratio [aHR] 2.14; 95% confidence interval [CI] 1.70-2.70), with similar risks across strata of viral load and immunosuppression. Current and previous tuberculosis were associated with COVID-19 death (aHR [95%CI] 2.70 [1.81-4.04] and 1.51 [1.18-1.93] respectively). The SMR for COVID-19 death associated with HIV was 2.39 (95%CI 1.96-2.86); population attributable fraction 8.5% (95%CI 6.1-11.1).

Conclusion: While our findings may over-estimate HIV- and tuberculosis-associated COVID-19 mortality risks due to residual confounding, both HIV and current tuberculosis were independently associated with increased COVID-19 mortality. The associations between age, sex and other comorbidities and COVID-19 mortality were similar to other settings.
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http://dx.doi.org/10.1093/cid/ciaa1198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499501PMC
August 2020

Use of seasonal influenza and pneumococcal polysaccharide vaccines in older adults to reduce COVID-19 mortality.

Vaccine 2020 07 19;38(34):5398-5401. Epub 2020 Jun 19.

Centre for Mathematical Modelling of Infectious Disease, Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.

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http://dx.doi.org/10.1016/j.vaccine.2020.06.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303659PMC
July 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

HIV infection is associated with increased meningococcal carriage acquisition amongst first-year students in two South African universities.

Clin Infect Dis 2020 May 5. Epub 2020 May 5.

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

Background: Invasive meningococcal disease clusters occur amongst university students and may reflect higher carriage prevalence amongst this population. We aimed to measure meningococcal carriage prevalence, acquisition and risk factors amongst first-year university students in South Africa, a middle-income country.

Methods: In summer to autumn 2017, after consenting to participate, we collected oropharyngeal swabs and questionnaires on carriage risk factors and tested students for HIV infection at two universities, during registration week (survey one) and 6-8 weeks later (survey two). Meningococci were detected by culture and polymerase chain reaction.

Results: We enrolled 2120 students at registration. Mean age was 18.5 years, 59% (1252/2120) were female and 0.8% (16/1984) were HIV-infected. Seventy-eight percent of students returned for survey two (1655/2120).Amongst the cohort, carriage prevalence was 4.7% (77/1655) at registration; increasing to 7.9% (130/1655) at survey two: 5.0% (83) acquired new carriage, 2.8% (47) had persistent carriage, 1.8% (30) cleared the initial carriage and 90.3% (1495) remained carriage-free. At both surveys, non-genogroupable meningococci predominated, followed by genogroups Y, B, W and C. On multinomial analysis risk factors for carriage acquisition included attending nightclubs (adjusted relative risk ratio (aRRR) 2.1 (95%CI=1.1-4.0)), having intimate kissing partners (aRRR 1.8 (95%CI=1.1-2.9)) and being HIV-infected (aRRR 5.0 (95%CI=1.1-24.4)).

Conclusion: Meningococcal carriage amongst first-year university students increased after two months. Social-behavioural risk factors were associated with increased carriage for all analyses. HIV-infection was associated with carriage acquisition. Until vaccination programmes become mandatory in South African universities, data suggest that HIV-infected students could benefit most from meningococcal vaccination.
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http://dx.doi.org/10.1093/cid/ciaa521DOI Listing
May 2020

Global burden of respiratory infections associated with seasonal influenza in children under 5 years in 2018: a systematic review and modelling study.

Lancet Glob Health 2020 04 20;8(4):e497-e510. Epub 2020 Feb 20.

Centre for Global Health, Usher Institute, Edinburgh Medical School, University of Edinburgh, Edinburgh, UK. Electronic address:

Background: Seasonal influenza virus is a common cause of acute lower respiratory infection (ALRI) in young children. In 2008, we estimated that 20 million influenza-virus-associated ALRI and 1 million influenza-virus-associated severe ALRI occurred in children under 5 years globally. Despite this substantial burden, only a few low-income and middle-income countries have adopted routine influenza vaccination policies for children and, where present, these have achieved only low or unknown levels of vaccine uptake. Moreover, the influenza burden might have changed due to the emergence and circulation of influenza A/H1N1pdm09. We aimed to incorporate new data to update estimates of the global number of cases, hospital admissions, and mortality from influenza-virus-associated respiratory infections in children under 5 years in 2018.

Methods: We estimated the regional and global burden of influenza-associated respiratory infections in children under 5 years from a systematic review of 100 studies published between Jan 1, 1995, and Dec 31, 2018, and a further 57 high-quality unpublished studies. We adapted the Newcastle-Ottawa Scale to assess the risk of bias. We estimated incidence and hospitalisation rates of influenza-virus-associated respiratory infections by severity, case ascertainment, region, and age. We estimated in-hospital deaths from influenza virus ALRI by combining hospital admissions and in-hospital case-fatality ratios of influenza virus ALRI. We estimated the upper bound of influenza virus-associated ALRI deaths based on the number of in-hospital deaths, US paediatric influenza-associated death data, and population-based childhood all-cause pneumonia mortality data in six sites in low-income and lower-middle-income countries.

Findings: In 2018, among children under 5 years globally, there were an estimated 109·5 million influenza virus episodes (uncertainty range [UR] 63·1-190·6), 10·1 million influenza-virus-associated ALRI cases (6·8-15·1); 870 000 influenza-virus-associated ALRI hospital admissions (543 000-1 415 000), 15 300 in-hospital deaths (5800-43 800), and up to 34 800 (13 200-97 200) overall influenza-virus-associated ALRI deaths. Influenza virus accounted for 7% of ALRI cases, 5% of ALRI hospital admissions, and 4% of ALRI deaths in children under 5 years. About 23% of the hospital admissions and 36% of the in-hospital deaths were in infants under 6 months. About 82% of the in-hospital deaths occurred in low-income and lower-middle-income countries.

Interpretation: A large proportion of the influenza-associated burden occurs among young infants and in low-income and lower middle-income countries. Our findings provide new and important evidence for maternal and paediatric influenza immunisation, and should inform future immunisation policy particularly in low-income and middle-income countries.

Funding: WHO; Bill & Melinda Gates Foundation.
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http://dx.doi.org/10.1016/S2214-109X(19)30545-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083228PMC
April 2020

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

Influenza Other Respir Viruses 2020 05 14;14(3):266-273. Epub 2020 Feb 14.

National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.

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.
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http://dx.doi.org/10.1111/irv.12724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182598PMC
May 2020

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

Euro Surveill 2019 Nov;24(45)

Health Intelligence Team, Institute of Environmental Science and Research, Wellington, New Zealand.

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.
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http://dx.doi.org/10.2807/1560-7917.ES.2019.24.45.1900645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852316PMC
November 2019

Vaccinating Mothers to Protect Their Babies Against Influenza.

J Infect Dis 2020 01;221(1):5-7

Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, Johannesburg, South Africa.

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http://dx.doi.org/10.1093/infdis/jiz387DOI Listing
January 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

Healthcare seeking behaviour for common infectious syndromes among people in three administrative regions of Johannesburg, South Africa, 2015: a cross-sectional study.

Pan Afr Med J 2019 3;33:159. Epub 2019 Jul 3.

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

Introduction: Hospital-based surveillance programs only capture people presenting to facilities and may underestimate disease burden. We conducted a healthcare utilisation survey to characterise healthcare-seeking behaviour among people with common infectious syndromes in the catchment areas of two sentinel surveillance hospitals in Johannesburg, South Africa.

Methods: A cross-sectional survey was conducted within three regions of Johannesburg from August to November 2015. Premises were randomly selected from an enumerated list with data collected on household demographics and selected syndromes using a structured questionnaire. Fisher's exact or chi-square tests were used to determine association of characteristics among different regions.

Results: Of 3650 selected coordinates, 3358 were eligible dwellings and 2930 (87%) households with 9850 individuals participated. Four percent of participants (431/9850) reported influenza-like illness (ILI) in the last 30 days; equal numbers of participants (0.2%, 20/9850) reported pneumonia or tuberculosis symptoms in the last year and <1% reported diarrhoea or meningitis symptoms. Sixty eight percent (295/431) of participants who reported ILI, 75% (6/8) of children with diarrhoea and all participants who reported pneumonia (20), tuberculosis (20) or meningitis (6) sought healthcare. For all syndromes most sought care at registered healthcare providers. Of these only 10% (24/237) attended sentinel hospitals, predominantly those that lived closer to the hospitals. In contrast, of patients with meningitis, 50% (3/6) sought care at sentinel hospitals.

Conclusion: Patterns of seeking healthcare differed by syndrome and distance from facilities. Surveillance programs are still relevant in collecting information on infectious syndromes and reflect a proportion of the hospital's catchment area.
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http://dx.doi.org/10.11604/pamj.2019.33.159.18461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756806PMC
October 2019

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

The epidemiological signature of influenza B virus and its B/Victoria and B/Yamagata lineages in the 21st century.

PLoS One 2019 12;14(9):e0222381. Epub 2019 Sep 12.

Netherlands Institute for Health Services Research (Nivel), Utrecht, The Netherlands.

We describe the epidemiological characteristics, pattern of circulation, and geographical distribution of influenza B viruses and its lineages using data from the Global Influenza B Study. We included over 1.8 million influenza cases occurred in thirty-one countries during 2000-2018. We calculated the proportion of cases caused by influenza B and its lineages; determined the timing of influenza A and B epidemics; compared the age distribution of B/Victoria and B/Yamagata cases; and evaluated the frequency of lineage-level mismatch for the trivalent vaccine. The median proportion of influenza cases caused by influenza B virus was 23.4%, with a tendency (borderline statistical significance, p = 0.060) to be higher in tropical vs. temperate countries. Influenza B was the dominant virus type in about one every seven seasons. In temperate countries, influenza B epidemics occurred on average three weeks later than influenza A epidemics; no consistent pattern emerged in the tropics. The two B lineages caused a comparable proportion of influenza B cases globally, however the B/Yamagata was more frequent in temperate countries, and the B/Victoria in the tropics (p = 0.048). B/Yamagata patients were significantly older than B/Victoria patients in almost all countries. A lineage-level vaccine mismatch was observed in over 40% of seasons in temperate countries and in 30% of seasons in the tropics. The type B virus caused a substantial proportion of influenza infections globally in the 21st century, and its two virus lineages differed in terms of age and geographical distribution of patients. These findings will help inform health policy decisions aiming to reduce disease burden associated with seasonal influenza.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0222381PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6742362PMC
March 2020

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

Pan Afr Med J 2019 21;33:42. Epub 2019 May 21.

Centre for Respiratory Diseases and Meningitis (CRDM), National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service (NHLS), Johannesburg, South Africa.

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.
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http://dx.doi.org/10.11604/pamj.2019.33.42.16666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658148PMC
September 2019

Global patterns in monthly activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus: a systematic analysis.

Lancet Glob Health 2019 08;7(8):e1031-e1045

Centre for Global Health Research, University of Edinburgh, Edinburgh, UK. Electronic address:

Background: Influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus are the most common viruses associated with acute lower respiratory infections in young children (<5 years) and older people (≥65 years). A global report of the monthly activity of these viruses is needed to inform public health strategies and programmes for their control.

Methods: In this systematic analysis, we compiled data from a systematic literature review of studies published between Jan 1, 2000, and Dec 31, 2017; online datasets; and unpublished research data. Studies were eligible for inclusion if they reported laboratory-confirmed incidence data of human infection of influenza virus, respiratory syncytial virus, parainfluenza virus, or metapneumovirus, or a combination of these, for at least 12 consecutive months (or 52 weeks equivalent); stable testing practice throughout all years reported; virus results among residents in well-defined geographical locations; and aggregated virus results at least on a monthly basis. Data were extracted through a three-stage process, from which we calculated monthly annual average percentage (AAP) as the relative strength of virus activity. We defined duration of epidemics as the minimum number of months to account for 75% of annual positive samples, with each component month defined as an epidemic month. Furthermore, we modelled monthly AAP of influenza virus and respiratory syncytial virus using site-specific temperature and relative humidity for the prediction of local average epidemic months. We also predicted global epidemic months of influenza virus and respiratory syncytial virus on a 5° by 5° grid. The systematic review in this study is registered with PROSPERO, number CRD42018091628.

Findings: We initally identified 37 335 eligible studies. Of 21 065 studies remaining after exclusion of duplicates, 1081 full-text articles were assessed for eligibility, of which 185 were identified as eligible. We included 246 sites for influenza virus, 183 sites for respiratory syncytial virus, 83 sites for parainfluenza virus, and 65 sites for metapneumovirus. Influenza virus had clear seasonal epidemics in winter months in most temperate sites but timing of epidemics was more variable and less seasonal with decreasing distance from the equator. Unlike influenza virus, respiratory syncytial virus had clear seasonal epidemics in both temperate and tropical regions, starting in late summer months in the tropics of each hemisphere, reaching most temperate sites in winter months. In most temperate sites, influenza virus epidemics occurred later than respiratory syncytial virus (by 0·3 months [95% CI -0·3 to 0·9]) while no clear temporal order was observed in the tropics. Parainfluenza virus epidemics were found mostly in spring and early summer months in each hemisphere. Metapneumovirus epidemics occurred in late winter and spring in most temperate sites but the timing of epidemics was more diverse in the tropics. Influenza virus epidemics had shorter duration (3·8 months [3·6 to 4·0]) in temperate sites and longer duration (5·2 months [4·9 to 5·5]) in the tropics. Duration of epidemics was similar across all sites for respiratory syncytial virus (4·6 months [4·3 to 4·8]), as it was for metapneumovirus (4·8 months [4·4 to 5·1]). By comparison, parainfluenza virus had longer duration of epidemics (6·3 months [6·0 to 6·7]). Our model had good predictability in the average epidemic months of influenza virus in temperate regions and respiratory syncytial virus in both temperate and tropical regions. Through leave-one-out cross validation, the overall prediction error in the onset of epidemics was within 1 month (influenza virus -0·2 months [-0·6 to 0·1]; respiratory syncytial virus 0·1 months [-0·2 to 0·4]).

Interpretation: This study is the first to provide global representations of month-by-month activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus. Our model is helpful in predicting the local onset month of influenza virus and respiratory syncytial virus epidemics. The seasonality information has important implications for health services planning, the timing of respiratory syncytial virus passive prophylaxis, and the strategy of influenza virus and future respiratory syncytial virus vaccination.

Funding: European Union Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU).
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http://dx.doi.org/10.1016/S2214-109X(19)30264-5DOI Listing
August 2019

Live attenuated influenza vaccines for African children.

Lancet Respir Med 2019 08 21;7(8):641-643. Epub 2019 Jun 21.

WHO Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.

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http://dx.doi.org/10.1016/S2213-2600(19)30145-6DOI Listing
August 2019

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