With the inclusion of new member states, nearly half of the world's population today residence in the BRICS + countries. However, no studies have systematically assessed the disease burden caused by lower respiratory tract infections (LRI) in these countries. Using data from the Global Burden of Disease Study (GBD) 2019 and age-period-cohort models, we estimate the temporal patterns, causes, and risk determinants of LRI burden between 1990 and 2019. The findings showed BRICS + experienced a total of 256821260 LRI events, accounting for 52.5% of the global incidence (488902504), accounting for 34.2% of the global LRI deaths [2493199 (2736184 to 2268183)] In 2019. The age standardized mortality rate of LRIs in BRICS + countries ranged from 13.8 to 86.4 cases per 100,000 people. Local drift showed that the improvement was most pronounced in children. In terms of numbers, pneumococci are the common LRI type in all countries. In terms of risk factors, countries show strong heterogeneity. From 1990 to 2019, the burden of LRI generally decreased as SDI increased. The result shows that BRICS countries should strengthen cooperation and exchanges in health and provide better experience for other developing countries to reduce the burden of LRI.
Research Article
Temporal Patterns, Causes, and Risk Determinants of Lower Respiratory Infections in BRICS+ Countries: A Longitudinal Inter-Country Assessment of Disease Burdens
https://doi.org/10.21203/rs.3.rs-4885447/v1
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Global burden of disease
Lower respiratory infection
Etiology
Risk factor
BRICS
Lower respiratory infections (LRIs) significantly contribute to death and disability globally, notably in children under five [1]. In developing countries, the disease burden of lower respiratory tract infections is higher due to lack of medical resources, environmental degradation, and weak awareness of disease prevention among the population [2].
After the 2023 BRICS South Africa Conference Declaration was released, BRICS + has now included ten member countries distributed in different continents, including 3,567,960,329 population in 2019, accounting for nearly 50% of the world's population [3–4]. Most of the BRICS + countries are developing countries. Previous studies have proven that lower SDI is related to higher LRI burden [2]. Due to their huge population base and representation in developing countries, changes in the LRI of the BRICS + countries can It better reflects the epidemiological situation of infectious diseases in developing countries and becomes an important reference for monitoring health inequality.
In this comparative study across BRICS+, we explore the burden of LRIs and its trends, etiologies, and risk factors between 1990 and 2019.
Data sources, variables and analytical sampl e
We utilised data from the Global Burden of Disease (GBD) 2019 study (GBD 2019) covering 21 geographical regions and 204 countries between 1990 and 2019[5]. The BRICS + is an intergovernmental organisation comprising ten countries, including Brazil, Russia, India, China, South Africa, Ethiopia, The United Arab Emirates, Kingdom of Saudi Arabia, the Islamic Republic of Iran and the Arab Republic of Egypt. LRI were defined utilising the International Classification of Diseases (ICD), which included ICD-9 codes 073.0-073.6, 079.82, 466–469, 480–489, 513.0, and 770.0 and ICD10 codes A48.1, J09-J22, J85.1, P23-P23.9, and U04. The etiologies included influenza, respiratory syncytial virus, Streptococcus pneumoniae, and Haemophilus influenzae type-b. We studied 14 critical risk factors attributable to LRI deaths, including null access to handwashing, ambient particulate matter pollution, household air pollution from solid fuels, highest and lowest temperature, non-exclusive breastfeeding, child underweight, child wasting, child stunting, short gestation, low birth weight, smoking, secondhand smoke, and alcohol use [5, 6]. GBD2019 defined an LRI episode as an infection directly caused by the identified pathogen. Input data from the GBD 2019 included all data used in GBD 2017, data from a systematic review, and inpatient data [5]. The non-fatal burden of LRIs was modelled using a Bayesian meta-regression modeling framework (i.e., Dis Mod-MR). Details of the methods have been published elsewhere [1, 5]. Our main outcomes referred to the disability adjusted life year (DALYs) and the Sociodemographic Index (SDI). The SDI is the geometric mean, ranging between 0 and 1 of different indices, including fertility rate under the age of 25, mean education for those ages 15 and older and lagged distributed income per capita [7, 8].
Statistical analyses
We analyzed the association between DALYs SDI. Data outcomes were described in terms of absolute numbers and age-standardized rates per 100,000 populations following 95% uncertainty interval (UI) following a static (i.e., period-specific) and dynamic (i.e., changes over time) levels. We calculated the average annual percentage change (AAPC) in terms of age-standardized incidence rates, number of deaths, and DALYs attributable to LRIs in 10 BRICS countries. We estimated the impact of age, period, and birth cohort on chronic disease mortality using an age-period-cohort (APC) model; previously utilized to analyze mortality trends from infectious diseases [9, 10]. We obtained the estimated parameters from the age-period-cohort Web Tool designed by the National Cancer Institute of the United States and used central age groups (i.e., 50–54 years) for the 2000–2004 period, and 1950–1954 cohort as reference [11, 12, 13]. APC models were tested using Wald chi-squared test, and statistical significance was considered two-sided utilising p ≤ 0.05[6, 14, 15].
We used the Joinpoint (v 5.0) software for statistical analyses and R for data visualization v 4.3.1[16, 17].
Trends in LRI Incidence, Mortality and DALYs
In 2019, BRICS + experienced a total of 256821260 LRI events, accounting for 52.5% of the global incidence (488902504), an increase of 16.9% from 1990 (219640408 cases). The total number of deaths caused by LRI is 852668, accounting for 34.2% of the global LRI deaths [2493199 (2736184 to 2268183)], a decrease of 44.5% compared to 1990. In 2019, India reported the highest number of LRI deaths [433661 (381633, 489555)], followed by China [185264 (160993, 216218)]. The age standardized mortality rate of LRIs in BRICS + countries ranged from 13.8 to 86.4 cases per 100000 people, and the age standardized DALYs rate of LRIs was 343.1 to 2415.7 cases per 100000 people. Ethiopia [2415.7 (2067.8, 2845.7)], South Africa [2104.9 (1880.6, 2373.1)], and India [1631.6 (1411.2, 1903.5)] had the highest figures. On the contrary, China [343.1 (304.6, 391.6)], Iran [359 (326.5, 390.5)], and Russia [603.5 (527.2, 684.2)] had the lowest numbers (Table 1, Fig. 1).
Table 1. Incidence, deaths and DALYs for LRI in 2019 and the average annual percent change during the period 1990–2019 Notes: Data were sourced from the GBD study. DALYs = Disability-adjusted life years. LRI = Lower respiratory infections. UI = uncertainty interval. ASR = Age-standardized rates. AAPC = Average Annual Percent Change.
Almost all countries, except for Russia with an increase of 0.48% per year (95% CI: 0.07 to 0.89), showed a decrease in LRI deaths overtime, with China displaying the most significant decrease of-4.72% per year (95% CI: -4.89 to -4.56) (Table S1).
When dividing by age group, local drift is below zero for all age groups under 19 years old, indicating an improvement in LRI mortality rates in children and adolescents. In China, progress is most significant across all age groups. The most significant progress was observed in infants and young children aged 0 to 4, with a score of -10.1% per year (95% CI: -10.26 to -9.93) (Table S1).
From 1990 to 2019, the percentage change of age standardized incidence rate in all BRICS + countries decreased, with China [average annual percent change(AAPC): -2.06 (95% CI-2.1, -2.03)], Ethiopia [AAPC: -1.68 (-1.78, -1.58) and Iran [AAPC: -1.45 (-1.53, -1.37)] having the largest decline. In contrast, the Russia [AAPC: -0.49 (-0.63, -0.36)] and South Africa [AAPC: -0.5 (-0.56, -0.45)] had the smallest reductions.
Between 1990 and 2019, there was no increase in DALYs (Disability-Adjusted Life Years) rates in any country. Similarly, China [AAPC: -7.7 (-7.88, -7.52)], Egypt [AAPC: -5.14 (-5.47, -4.82)], and Iran [AAPC: -5.01 (-5.16, -4.86)] had the largest reductions in standardized disability adjusted life rates during the same period (Table 1).
Individual Level-Age-Period-Cohort Effect Analysis
Figure 2 illustrates the age, period, and cohort effects of sex specific LRI mortality rate. After controlling for period and cohort effects, we found that LRI mortality rate was highest between 0–4 years old populations, followed by a rapid decline with age until it stabilized at a low level at 60 years. After this time point, the curve showed a gradual increase in LRI deaths among individuals > 60 years of age. LRI mortality rate was heterogeneous among countries. Even though all nations suffered higher death rates in youngest and oldest groups, Ethiopia experienced a high peak of LRI death in the 0–5 years old age group and South Africa in the > 75 group. China displayed the second highest under-5 mortality but lowest among > 75 age. The overall trend of relative risk (RR) of LRIs is declining in BRICS + countries, although there are fluctuations of period RR in Russia and South Africa and cohort RR for the Middle East and North Africa (NAME) countries. notably in China where LRI period RR significantly dropped from 1.64 to 0.5. This decline is observed for both sexes, particularly among Chinese women. Countries like China, Ethiopia, Iran, and India have seen marked LRI risk reductions compared to cohorts born before 1950. Wald Chi Square tests confirmed these trends in the APC model are statistically significant (all p < 0.001).
Association with SDI
From 1990 to 2019, with socio-economic development, the burden of LRIs generally declined. Countries such as South Africa and Egypt have a higher burden than expected, while others such as Iran have a lower burden than expected.
Notes: Expected values based on the Socio-demographic Index (SDI) and disease rates in all locations are shown in Fig. 3 (black line). Each point shows the observed age-standardised DALY rate for each country in 2019.
Etiology and risk factors
In both 1990 and 2019, the most common death etiology reported was pneumococcal. In terms of risk factors, data from different countries and years reflect obvious differences. In 1990, five of the ten countries had the highest proportion of child waste; followed by household air pollution from solid fuels, which had the highest proportion of four countries. With the general decline in mortality rates, the contribution of risk factors has undergone structural changes in most countries. In 2019, the risk factor with the highest proportion in six countries was ambient particulate matter pollution. In addition, the proportion of smoking in Brazil and Russia increased to the largest factor. In 1990, no country had the largest proportion of smoking. The proportion of household air pollution from solid fuels in Ethiopia and the proportion of ambient particulate matter pollution in United Arab Emirates are always the largest.
We showed that in 2019, the total death toll caused by LRI was 852668, accounting for 34.2% of the global LRI deaths [2493199 (2736184 to 2268183)]. However, it is encouraging that the ASMR and burden from LRIs in the BRICS + countries has improved (decreased) since 1990. Consistent with prior research, LRI's impact was marginally less in women than in men [18]. Pneumococci emerged as the leading cause of LRI-related deaths and DALYs in every country. Moreover, countries with higher SDI typically exhibited lower age-standardized DALY rates from LRIs. Within the BRICS + countries, there are significant differences between countries in rates and secular trends. Below, we provide conclusions at the regional/country sublevel.
In 2019, Ethiopia had the largest number of LRI deaths and the highest disease burden among BRICS + countries, and although the period and cohort models showed a significant improvement in LRI mortality in Ethiopia in recent years, the age model showed that the relative risk of 0–4 years is still extremely high. For the pathogens, consistent with the GBD2015 data, the number of deaths due to Streptococcus pneumoniae still exceeds the sum of other LRI causes [19]. Local drift shows the most pronounced decline in child mortality between 0–4 years. In addition to the increase in health facilities and health personnel, this may be related to the recent implementation of IMCI in Ethiopia since 1997, especially the inclusion of 10-valent pneumococcal conjugate vaccines (pneumococcal conjugate vaccine, PCVs) in 2011 [20]. However, national analysis showed that LRI remains the third leading cause of death in Ethiopia, with particularly severe effects on children under 5 years and mainly pastoralist areas, where vaccination rates are generally low [19–20]. Moreover, local drift showed a decrease in mortality in people over 65 years, lower than the national average for net drift, and a lower reduction in mortality in men than in women. In terms of risk factors, Household air pollution from solid fuels, limited access to handwashing facility and child wasting are the main risk factors. National-level analysis showed that newborns in Ethiopia had higher rates of stunting, child underweight and wasting in rural areas than in urban areas [19–21]. These regional differences and SES differences also present challenges for the prevention and treatment of LRI.
The cohort analysis indicated a reduced relative risk for children aged 0–4 years in South Africa compared to Ethiopia, aligning with other sub-Saharan nations and recent studies [21]. However, South Africa experiences a marked increase in mortality rates among the elderly, without significant declines over time.
Notably, South Africa, among ten reviewed countries, faces a substantial health burden compared with other BRICS + countries with similar SDI, impacted by factors such as high HIV prevalence, industrial air pollution, and chronic respiratory diseases, all detrimental to preventing and treating LRI in the medical system. [22–24]. The compounded effects of local HIV prevalence, aging population, mining-related pollution, and ineffective tobacco control underscore the complexities facing LRI prevention and management in the region, On the bright side, Over the past years, South Africa has concentrated resources on the treatment of infectious diseases, and we noticed that LRI mortality improved around 2005. This time point is close to the turning point of HIV-positive tuberculosis in other studies. these investments seem to have been rewarded. [25–28]
Among the BRICS + countries, four member countries are located in the Middle East and North Africa (NAME) region, including Iran, Saudi Arabia, Egypt, UAE. Among the four analyzed countries, Iran exhibits the lowest mortality and disease burden, while Egypt faces the highest. Notably, both countries have experienced significant reductions in death rates over the last three decades. Iran's relatively lower burden, compared with other BRICS + countries with similar SDI, may reflect its robust primary healthcare system [29]. Common risk factors across these nations include high levels of air pollution and widespread tobacco use, including passive smoking. Given the elevated smoking rates and rising environmental pollution, particularly in NAME regions [30–31], enhanced focus on air quality and stricter adherence to the WHO Framework Convention on Tobacco Control (WHO FCTC), especially regarding hookah use [32–35], is imperative. Additionally, the cross-border population mobility and mass gathering and presents a challenge to health planners, geopolitical conflicts and potential sanctions Adverse impact on NAME healthcare infrastructures, underscoring the necessity for policies ensuring consistent vaccine and medical supply chains [36–38].
Between 1990 and 2019, Brazil's increase in LRI-related deaths primarily stemmed from demographic shifts, including population growth and aging. Despite this, the country observed a decline in CRD mortality due to improvements across different time periods and birth cohorts. Recent years have seen mortality improvements, partially attributed to expanded access to the influenza vaccine since 1999 and the introduction of the 10-valent pneumococcal conjugate vaccine (PCV 10) in the Unified Health System (SUS) in 2010, though the rollout for the elderly was not simultaneous. [39]
In 2019, smoking emerged as a significant risk factor in Brazil. However, the implementation of the Framework Convention on Tobacco Control in 2006, the No Tobacco Law in 2014, and subsequent tobacco control measures have led to a roughly 60% decrease in tobacco usage from 1998 to 2013. Despite this success, the rate of decline in smoking has slowed in recent years.[40–42] These findings underscore the critical need for ongoing tobacco control policies to manage respiratory diseases in Brazil's aging population.
In China, both local drift and net drift showed significant improvements observed for all ages and sex, while the relative risk decline for women was more significant in the period and cohort models. The fast economic growth, increasing access to child healthcare, improvement of child nutrition, and health promotion may be a driver[6, 43]. During the study period, the socio-economic progress, the popularization of vaccines, the progress of basic public health services, and the new rural cooperative medical system contributed to the improvement of LRI mortality in China [43–46] The Chinese government issued a series of policies to control risk factors LRI. Including promoting the emission control of industrial production and comprehensive air quality testing, and the promotion of clean fuels in rural areas [47]. Meanwhile, smoking rates in both men and women have decreased since 1990, However, current tobacco dependence is still very common in China [4], which highlights the need to further promote tobacco restriction measures to raise public awareness of the harm of tobacco. Moreover, given that the current cost-effectiveness of the 13-valent vaccine in China is confirmed, the health sector could continue to popularize vaccination to further reduce the incidence of LRI in China [49].
In 2019, India reported the highest number of deaths among the BRICS + nations. A consistent decline in mortality risk over the past thirty years, as observed in both Period and Cohort models, can be attributed to improved socio-economic conditions. Yet, India’s public healthcare system continues to confront significant hurdles.[50] Sociodemographic analyses reveal a high prevalence of infectious diseases among marginalized groups, with disease burden and risk factors diverging substantially across states.[51–52] Concurrently, India is undergoing an epidemiological transition, with CRD increasingly impacting lower respiratory infections amid an aging population and extended life expectancy. This shift underscores the urgent need for bolstered primary healthcare systems and mitigating risk factors. [53–54] The Indian government's recent initiatives, such as Ayushman Bharat and the National Digital Health Mission (NDHM) launched in 2021, aim to address health disparities. However, assessing the effectiveness of these programs will require time. Ongoing epidemiological surveillance is essential for the effectiveness of policy advancement.
In 1990, Russia started with the lowest baseline mortality rate; however, between 1990 and 2019, there was a slight uptrend in LRI mortality, primarily attributed to increased rates in adults aged 20–80. This rise aligns with the healthcare disruptions during the post-Soviet era, particularly affecting the 1970–1995 cohorts.[55] Notably, risk factors such as smoking and alcohol consumption surged until the implementation of effective tobacco control measures in 2008. [56] Recent declines in smoking rates post-2000 have likely contributed to a decreased RR of mortality in Russia's Period model. To further combat LRI burden, Russian health policymakers must persist in targeting adult lifestyle risk factors, emphasizing tobacco and alcohol reduction.
Our study has some shortcomings. First, we have limited data in some sites, especially in Ethiopia and Elderly population. which leads to a large uncertainty interval (UI) and affects the interpretation of our results. Second, this study included the clinical diagnosis of LRI without further laboratory or imaging evaluation. It requires future researchers could conduct further epidemiological investigations and provide a more detailed analysis of the disease burden of LRI. The period and age intervals should be fixed and equal in the APC tool, data of people aged ≥ 95 years could not be analyzed because of the data availability (they were merge to one age group in GBD2019) However, to our knowledge, this is the first country-level study analyzing the burden of LRI, its underlying etiology, and risk factors after the expansion in BRICS + countries.
We conclude that the burden of LRI in the ten BRICS + countries has generally declined over the last three decades as the socioeconomic status has increased. But we still find serious health inequalities within and between BRICS + countries, and differences in major public health problems and major risk factors across these countries. Before the five new countries joined, the BRICS + countries had already launched a series of cooperation and issued declarations on public health issues. In 2016, the BRICS + health ministers meeting in Delhi made security to promote the supply of vaccines and drugs, improve the epidemic detection, solve the problem of antimicrobial drug resistance major issues such as strong commitment, and reiterated the support of the world health organization framework convention on tobacco control, Xiamen declaration in 2017 emphasizes to strengthen the role of the BRICS + countries in global health governance, improve the ability to fight infectious diseases, strengthen the health system and financing [57]. Given the large size of BRICS + economies and their important demonstration effect for other developing countries, whatever happens within BRICS + is likely to drive and shape global trends [58–59]. We call for broader international cooperation and more focus on evidence reflecting global health inequalities to get closer to our vision of reducing all preventable deaths to zero in the 2030 Agenda for Sustainable Development by 2030.
Funding
This research received no external funding.
Competing interests
The authors declare that there is no conflict of interest.
Availability of data and materials
The data used for these analyses are all publicly available at http://ghdx.healthdata.org/gbd-results-tool. This study is based on publicly available data and solely reflects the opinions of its authors and not that of the Institute for Health Metrics and Evaluation.
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The authors declare no competing interests.