Data on influenza community burden and transmission are important to plan interventions especially in resource-limited settings. However, data are limited, particularly from low-income and ...middle-income countries. We aimed to evaluate the community burden and transmission of influenza in a rural and an urban setting in South Africa.
In this prospective cohort study approximately 50 households were selected sequentially from both a rural setting (Agincourt, Mpumalanga Province, South Africa; with a health and sociodemographic surveillance system) and an urban setting (Klerksdorp, Northwest Province, South Africa; using global positioning system data), enrolled, and followed up for 10 months in 2017 and 2018. Different households were enrolled in each year. Households of more than two individuals in which 80% or more of the occupants agreed to participate were included in the study. Nasopharyngeal swabs were collected twice per week from participating household members irrespective of symptoms and tested for influenza using real-time RT-PCR. The primary outcome was the incidence of influenza infection, defined as the number of real-time RT-PCR-positive episodes divided by the person-time under observation. Household cumulative infection risk (HCIR) was defined as the number of subsequent infections within a household following influenza introduction.
81 430 nasopharyngeal samples were collected from 1116 participants in 225 households (follow-up rate 88%). 917 (1%) tested positive for influenza; 178 (79%) of 225 households had one or more influenza-positive individual. The incidence of influenza infection was 43·6 (95% CI 39·8–47·7) per 100 person-seasons. 69 (17%) of 408 individuals who had one influenza infection had a repeat influenza infection during the same season. The incidence (67·4 per 100 person-seasons) and proportion with repeat infections (22 23% of 97 children) were highest in children younger than 5 years and decreased with increasing age (p<0·0001). Overall, 268 (56%) of 478 infections were symptomatic and 66 (14%) of 478 infections were medically attended. The overall HCIR was 10% (109 of 1088 exposed household members infected 95% CI 9–13%). Transmission (HCIR) from index cases was highest in participants aged 1–4 years (16%; 40 of 252 exposed household members) and individuals with two or more symptoms (17%; 68 of 396 exposed household members). Individuals with asymptomatic influenza transmitted infection to 29 (6%) of 509 household contacts. HIV infection, affecting 167 (16%) of 1075 individuals, was not associated with increased incidence or HCIR.
Approximately half of influenza infections were symptomatic, with asymptomatic individuals transmitting influenza to 6% of household contacts. This suggests that strategies, such as quarantine and isolation, might be ineffective to control influenza. Vaccination of children, with the aim of reducing influenza transmission might be effective in African settings given the young population and high influenza burden.
US Centers for Disease Control and Prevention.
Summary Background The annual number of hospital admissions and in-hospital deaths due to severe acute lower respiratory infections (ALRI) in young children worldwide is unknown. We aimed to estimate ...the incidence of admissions and deaths for such infections in children younger than 5 years in 2010. Methods We estimated the incidence of admissions for severe and very severe ALRI in children younger than 5 years, stratified by age and region, with data from a systematic review of studies published between Jan 1, 1990, and March 31, 2012, and from 28 unpublished population-based studies. We applied these incidence estimates to population estimates for 2010, to calculate the global and regional burden in children admitted with severe ALRI in that year. We estimated in-hospital mortality due to severe and very severe ALRI by combining incidence estimates with case fatality ratios from hospital-based studies. Findings We identified 89 eligible studies and estimated that in 2010, 11·9 million (95% CI 10·3–13·9 million) episodes of severe and 3·0 million (2·1–4·2 million) episodes of very severe ALRI resulted in hospital admissions in young children worldwide. Incidence was higher in boys than in girls, the sex disparity being greatest in South Asian studies. On the basis of data from 37 hospital studies reporting case fatality ratios for severe ALRI, we estimated that roughly 265 000 (95% CI 160 000–450 000) in-hospital deaths took place in young children, with 99% of these deaths in developing countries. Therefore, the data suggest that although 62% of children with severe ALRI are treated in hospitals, 81% of deaths happen outside hospitals. Interpretation Severe ALRI is a substantial burden on health services worldwide and a major cause of hospital referral and admission in young children. Improved hospital access and reduced inequities, such as those related to sex and rural status, could substantially decrease mortality related to such infection. Community-based management of severe disease could be an important complementary strategy to reduce pneumonia mortality and health inequities. Funding WHO.
Influenza has long been a global public health priority because of the threat of another global pandemic. Although data are available for the annual burden of seasonal influenza in many developed ...countries, fewer disease burden data are available for low-income and tropical countries. In recent years, however, the surveillance systems created as part of national pandemic preparedness efforts have produced substantial data on the epidemiology and impact of influenza in countries where data were sparse. These data are leading to greater interest in seasonal influenza, including implementation of vaccination programs. However, a lack of quality data on severe influenza, nonrespiratory outcomes, and high-risk groups, as well as a need for better mathematical models and economic evaluations, are some of the major gaps that remain. These gaps are the focus of multilateral research and surveillance efforts that will strengthen global efforts in influenza control in the future.
Data on influenza epidemiology in HIV-infected persons are limited, particularly for sub-Saharan Africa, where HIV infection is widespread. We tested respiratory and blood samples from patients with ...acute lower respiratory tract infections hospitalized in South Africa during 2009-2011 for viral and pneumococcal infections. Influenza was identified in 9% (1,056/11,925) of patients enrolled; among influenza case-patients, 358 (44%) of the 819 who were tested were infected with HIV. Influenza-associated acute lower respiratory tract infection incidence was 4-8 times greater for HIV-infected (186-228/100,000) than for HIV-uninfected persons (26-54/100,000). Furthermore, multivariable analysis showed HIV-infected patients were more likely to have pneumococcal co-infection; to be infected with influenza type B compared with type A; to be hospitalized for 2-7 days or >7 days; and to die from their illness. These findings indicate that HIV-infected persons are at greater risk for severe illnesses related to influenza and thus should be prioritized for influenza vaccination.
The Streptococcus pneumoniae polysaccharide capsule plays a role in disease severity. We assessed the association of serotype with case-fatality ratio (CFR) in invasive pneumococcal disease (IPD) and ...meningitis in South Africa, 2012-2018 (vaccine era), using multivariable logistic regression by manual backward elimination. The most common serotypes causing IPD were 8 and 19A. In patients <15 years of age, serotypes associated with increased CFR in IPD, compared with serotype 8 and controlling for confounding factors, were 11A, 13, 19F, 15A, and 6A. None of these serotypes were associated with increased CFR in meningitis. Among IPD patients >15 years of age, serotype 15B/C was associated with increased CFR. Among meningitis patients of all ages, serotype 1 was associated with increased CFR. PCV13 serotypes 1, 3, 6A, 19A, and 19F should be monitored, and serotypes 8, 12F, 15A, and 15B/C should be considered for inclusion in vaccines to reduce deaths caused by S. pneumoniae.
Data on the economic burden of RSV-associated illness will inform decisions on the programmatic implementation of maternal vaccines and monoclonal antibodies. We estimated the cost of RSV-associated ...illness in fine age bands to allow more accurate cost-effectiveness models to account for a limited duration of protection conferred by short- or long-acting interventions.
We conducted a costing study at sentinel sites across South Africa to estimate out-of-pocket and indirect costs for RSV-associated mild and severe illness. We collected facility-specific costs for staffing, equipment, services, diagnostic tests, and treatment. Using case-based data we calculated a patient day equivalent (PDE) for RSV-associated hospitalizations or clinic visits; the PDE was multiplied by the number of days of care to provide a case cost to the healthcare system. We estimated the costs in 3-month age intervals in children aged < 1 year and as a single group for children aged 1-4 years. We then applied our data to a modified version of the World Health Organization tool for estimating the mean annual national cost burden, including medically and non-medically attended RSV-associated illness.
The estimated mean annual cost of RSV-associated illness in children aged < 5 years was US dollars ($)137,204,393, of which 76% ($111,742,713) were healthcare system incurred, 6% ($8,881,612) were out-of-pocket expenses and 13% ($28,225,.801) were indirect costs. Thirty-three percent ($45,652,677/$137,204,393) of the total cost in children aged < 5 years was in the < 3-month age group, of which 52% ($71,654,002/$137,204,393) were healthcare system incurred. The costs of non-medically attended cases increased with age from $3,307,218 in the < 3-month age group to $8,603,377 in the 9-11-month age group.
Among children < 5 years of age with RSV in South Africa, the highest cost burden was in the youngest infants; therefore, interventions against RSV targeting this age group are important to reduce the health and cost burden of RSV-associated illness.
Abstract
Background
The coronavirus disease 2019 (COVID-19) pandemic caused severe disruptions to healthcare in many areas of the world, but data remain scarce for sub-Saharan Africa.
Methods
We ...evaluated trends in hospital admissions and outpatient emergency department (ED) and general practitioner (GP) visits to South Africa’s largest private healthcare system during 2016–2021. We fit time series models to historical data and, for March 2020–September 2021, quantified changes in encounters relative to baseline.
Results
The nationwide lockdown on 27 March 2020 led to sharp reductions in care-seeking behavior that persisted for 18 months after initial declines. For example, total admissions dropped 59.6% (95% confidence interval CI, 52.4–66.8) during home confinement and were 33.2% (95% CI, 29–37.4) below baseline in September 2021. We identified 3 waves of all-cause respiratory encounters consistent with COVID-19 activity. Intestinal infections and non–COVID-19 respiratory illnesses experienced the most pronounced declines, with some diagnoses reduced 80%, even as nonpharmaceutical interventions (NPIs) relaxed. Non-respiratory hospitalizations, including injuries and acute illnesses, were 20%–60% below baseline throughout the pandemic and exhibited strong temporal associations with NPIs and mobility. ED attendances exhibited trends similar to those for hospitalizations, while GP visits were less impacted and have returned to pre-pandemic levels.
Conclusions
We found substantially reduced use of health services during the pandemic for a range of conditions unrelated to COVID-19. Persistent declines in hospitalizations and ED visits indicate that high-risk patients are still delaying seeking care, which could lead to morbidity or mortality increases in the future.
We found substantial declines in care seeking at all levels of clinical severity in South Africa’s largest private healthcare system. Non-COVID-19 respiratory illnesses and intestinal infections, followed by injuries, experienced the sharpest reductions and remained below baseline throughout the study.
Published data on the interaction between influenza and pulmonary tuberculosis (PTB) are limited. We aimed to estimate the influenza-associated mortality among individuals with PTB in South Africa ...from 1999-2009.
We modelled the excess influenza-associated mortality by applying Poisson regression models to monthly PTB and non-tuberculosis respiratory deaths, using laboratory-confirmed influenza as a covariate.
PTB deaths increased each winter, coinciding with influenza virus circulation. Among individuals of any age, mean annual influenza-associated PTB mortality rate was 164/100,000 person-years (n = 439). The rate of non-tuberculosis respiratory deaths was 27/100,000 (n = 1125) for HIV-infected and 5/100,000 (n = 2367) for HIV-uninfected individuals of all ages. Among individuals aged <65 years, influenza-associated PTB mortality risk was elevated compared to influenza-associated non-tuberculosis respiratory deaths in HIV-infected (relative risk (RR): 5.2; 95% CI: 4.6-5.9) and HIV-uninfected individuals (RR: 61.0; CI: 41.4-91.0). Among individuals aged ≥65 years, influenza-associated PTB mortality risk was elevated compared to influenza-associated non-tuberculosis respiratory deaths in HIV-uninfected individuals (RR: 13.0; 95% CI: 12.0-14.0).
We observed an increased risk of influenza-associated mortality in persons with PTB compared to non-tuberculosis respiratory deaths. If confirmed in other settings, our findings may support recommendations for active inclusion of patients with TB for influenza vaccination and empiric influenza anti-viral treatment of patients with TB during influenza epidemics.
Data on the burden and risk groups for influenza-associated mortality from Africa are limited. We aimed to estimate the incidence and risk-factors for in-hospital influenza-associated severe acute ...respiratory illness (SARI) deaths.
Hospitalised patients with SARI were enrolled prospectively in four provinces of South Africa from 2009-2013. Using polymerase chain reaction, respiratory samples were tested for ten respiratory viruses and blood for pneumococcal DNA. The incidence of influenza-associated SARI deaths was estimated at one urban hospital with a defined catchment population.
We enrolled 1376 patients with influenza-associated SARI and 3% (41 of 1358 with available outcome data) died. In patients with available HIV-status, the case-fatality proportion (CFP) was higher in HIV-infected (5%, 22/419) than HIV-uninfected individuals (2%, 13/620; p = 0.006). CFPs varied by age group, and generally increased with increasing age amongst individuals >5 years (p<0.001). On multivariable analysis, factors associated with death were age-group 45-64 years (odds ratio (OR) 4.0, 95% confidence interval (CI) 1.01-16.3) and ≥65 years (OR 6.5, 95%CI 1.2-34.3) compared to 1-4 year age-group who had the lowest CFP, HIV-infection (OR 2.9, 95%CI 1.1-7.8), underlying medical conditions other than HIV (OR 2.9, 95%CI 1.2-7.3) and pneumococcal co-infection (OR 4.1, 95%CI 1.5-11.2). The estimated incidence of influenza-associated SARI deaths per 100,000 population was highest in children <1 year (20.1, 95%CI 12.1-31.3) and adults aged 45-64 years (10.4, 95%CI 8.4-12.9). Adjusting for age, the rate of death was 20-fold (95%CI 15.0-27.8) higher in HIV-infected individuals than HIV-uninfected individuals.
Influenza causes substantial mortality in urban South Africa, particularly in infants aged <1 year and HIV-infected individuals. More widespread access to antiretroviral treatment and influenza vaccination may reduce this burden.
Temporal variation of respiratory syncytial virus (RSV) epidemics was recently reported to be determined by the dominant RSV subtype. However, when we repeated the analysis for 4 countries in the ...Northern and Southern Hemispheres, the dominant subtype did not seem to affect temporal variation of RSV epidemics.