Lower respiratory infections (LRIs) are one of the leading causes of death and disability-adjusted life-years (DALYs) worldwide, especially among children under 5 (Kassebaum et al. 2016; Wang et al. 2016). Since 1990, LRI has been the closest competitor of cardiovascular diseases as the top leading cause of DALYs in the Eastern Mediterranean Region (EMR) and the Arab world (Mokdad et al. 2014, 2016). Several factors, such as poverty, indoor and outdoor air pollution, malnutrition, smoking, chronic lung diseases, and delayed and inappropriate case management contribute to the high burden of LRI (Hadi 2003). Population-based measures of morbidity and mortality of LRI are scarce. Most of the available data are limited to children and are based on modeling approaches. Even fewer data are available for causative agents of LRI (Kovacs et al. 2015).
Rudan et al. estimated an incidence of 0.22 episodes of community-acquired pneumonia per child-year in children under 5 in low- and middle-income countries in 2010 (Rudan et al. 2013) The Child Health Epidemiology Reference Group (CHERG) estimated 0.26 episodes per child-year for the world and 0.28 for the World Health Organization’s (WHO) Eastern Mediterranean Region (EMR). These estimates translate to about 20 million cases of childhood pneumonia each year in the EMR, with approximately 10% of cases requiring hospitalization (Rudan et al. 2008). More than 99% of all LRI deaths occur in low- and middle-income countries. Although about 62% of children with severe LRI reach hospitals, more than 80% of all childhood LRI deaths take place outside the hospital setting (Nair et al. 2013; Tong 2013). Despite high levels of morbidity and mortality, the decreasing trend in LRI mortality rates has contributed to increasing life expectancy worldwide (Wang et al. 2016). Improvements in nutritional status (less malnutrition through attention to childhood and maternal nutritional status), increased uptake of vaccines such as immunization against Streptococcus pneumoniae (pneumococcus) and Haemophilus influenzae type b (Hib) in children and high-risk populations in EMRs, and improved access to antibiotics and supportive care have decreased the incidence and fatality of LRI in many countries (Williams and Shah 2012; Tong 2013).
In this study, we report findings from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) on LRI in the 22 countries of the EMR between 1990 and 2015. We describe the burden of LRI and a subset of specific etiologic pathogens, including pneumococcus, Hib, respiratory syncytial virus (RSV), and influenza virus, based on deaths, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs).
GBD 2015 covers 195 countries, 21 regions, and seven super-regions from 1990 to 2015 for 315 diseases and injuries and 79 risk factors. A counterfactual approach was used for estimating LRI etiologies, one of the methodological differences compared to GBD 2010. Detailed descriptions of the methodological approach for GBD 2015 have been published elsewhere (Forouzanfar et al. 2016; Kassebaum et al. 2016; Vos et al. 2016; Wang et al. 2016).
The EMR consists of 22 countries with different levels of gross national income (GNI) per capita. The low-income countries (LICs) are Afghanistan, Djibouti, Somalia, and Yemen. The middle-income countries (MICs) are Egypt, Iran, Iraq, Jordan, Lebanon, Libya, Morocco, Pakistan, Palestine, Sudan, Syria, and Tunisia. The high-income countries (HICs) are Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates (UAE).
All types of LRI (bronchitis, bronchiolitis, and pneumonia) were included in this study. We used the following International Classification of Diseases (ICD-10) codes (or their corresponding codes from earlier ICD versions) as equivalent to LRI: J09–J15.8, J16–J16.9, J20–J21.9, P23-P23.9, and Z25.1. The ICD-10 codes for etiologic categories of LRI included J09–J11.89 and Z25.1 for Influenza virus, J12.1 for RSV, J13, J13.0, J15.3, J15.4, and J15.6 for pneumococcus, J14 and J14.0 for Hib, and J12, J12.0, J12.2–J12.9, J15–J15.9, J15.5, J15.7, J15.8, J16–J16.9, J20–J21.9, and P23-P23.9 for other LRI. We did not include tuberculosis in this study; it has been classified as a separate item in GBD.
An analysis of available data on all-cause mortality for all countries was undertaken (Wang et al. 2016). For pathogen-specific mortality rates of LRI, we used a counterfactual approach based on the epidemiological concept of attributable mortality. The change in LRI was estimated assuming the condition that a specific pathogen was not present. We adopted different approaches to estimate bacterial and viral causes based on the available data. For pneumococcal and Hib LRI, we estimated the causal fraction from vaccine efficacy trials data. For RSV and influenza, we relied on observational studies that measured causal fractions among hospital admissions for LRI (Vos et al. 2016; Wang et al. 2016). We estimated the causal fractions among cases by country, age, and sex. To account for the higher case-fatality rate of bacterial versus viral LRI, we applied a relative case-fatality differential based on hospital data that included cases coded to the specific pneumonia causes. Our mortality estimates were used to calculate cause-specific YLLs for each age, sex, location, and calendar year.
To estimate LRI-related morbidity, a systematic review of studies on epidemiological indicators of LRI was done as part of the GBD standard methodology. We used 197 sources of data from EMR countries (46 for non-fatal outcomes and others for cause of death) which contained data on LRI. A list of all data sources is available on the Institute for Health Metrics and Evaluation’s website. (Institute for Health Metrics and Evaluation) A series of Bayesian meta-regression analyses through DisMod-MR 2.1 were used for disease modeling. Model-based epidemiological estimates in combination with disability weights were used to calculate cause-specific YLDs for each age, sex, location, and calendar year. DALYs were calculated through summation of YLLs and YLDs (Kassebaum et al. 2016; Vos et al. 2016).
We estimated burden of LRI attributable to childhood malnutrition (underweight, wasting, and stunting), non-exclusive breastfeeding, zinc deficiency, smoking, secondhand smoke exposure, household air pollution from solid fuels, and ambient air pollution as known LRI risk factors. Details on definitions and measures of age- and sex-specific relative risks of LRI for each of the risk factors are available elsewhere (Forouzanfar et al. 2016).
We report 95% uncertainty intervals (UI) for each estimate—such as rates or numbers of deaths or DALYs. We estimated UIs by taking 1000 samples from the posterior distribution of each quantity and using the 25th- and 975th-ordered draws of the uncertainty distribution.
LRI deaths decreased by 30.2% from 273,714 (95% UI 239,890–306,648) in 1990 to 191,114 (95% UI 170,934–210,705) in 2015 in EMR countries. In spite of the decrease, LRI is still the third-leading cause of death for all ages in 2015. The death rate per 100,000 was 74.0 (95% UI 64.8–82.9) in 1990 and decreased to 29.5 (95% UI 26.4–32.5) in 2015, a 60.1% reduction. The age-standardized death rate for LRI was 65.4 (95% UI 58.6–73.4) in 1990 and declined by 38.5% to 40.2 (95% UI 36.0–45.2) in 2015. In 2015, 4.8% (95% UI 4.3–5.2) of all deaths and 13.0% (95% UI 11.5–14.7) of under-5 deaths were due to LRI.
At the regional level, the highest death rates and numbers of deaths were among children under 5 years old, followed by those aged 65 years or older. However, there was considerable heterogeneity in the age pattern of LRI deaths between the countries of the EMR. In all high-income countries (Bahrain, Saudi Arabia, Kuwait, Oman, Qatar, and UAE), and some of the middle-income countries (Iran, Lebanon, Libya, Morocco, Palestine, Syria, and Tunisia), the LRI death rates among older age groups were greater than the mortality rates among children under 5 years. Death rates were 31.5 per 100,000 (95% UI 27.3–35.4) in men compared to 27.4 per 100,000 in women (95% UI 23.9–31.2) in the region. The LRI death rate was not different in EMR countries in boys versus girls under 5 (2015).
Figure 1 shows the age-standardized death rates for LRI by EMR country in 2013. Somalia, Djibouti, and Afghanistan had the highest death rates in the region.
Among the etiologic causes, pneumococcus had the highest mortality rate (16.6 per 100,000, 95% UI 10.0–22.9), followed by respiratory syncytial virus (1.5 per 100,000, 95% UI 0.9–2.4), Haemophilus influenzae type b (1.1 per 100,000, 95% UI 0.0–2.3), and influenza virus (0.8 per 100,000, 95% UI 0.5–1.2). Figure 2 demonstrates the contribution of different etiologic causes to LRI deaths by age.
The rate of YLLs per 100,000 population decreased by 69.5% from 5579 (95% UI 4,831–6,320) in 1990–1702 (95% UI 1,510–1,902) in 2015. However, LRI was still the third-leading cause of YLLs in 2015.
e-Table 1 shows age-standardized incidence rates of LRI in males and females of the EMR countries. The highest incidence rate was observed in Afghanistan and the lowest in Tunisia for both sexes. In all countries but Afghanistan, Bahrain, and Djibouti, the incidence rates were higher among men than women, with the highest male-to-female ratio in Iran and Libya.
The rate of YLDs per 100,000 decreased from 15.8 (95% UI 10.7–22.9) to 9.7 (95% UI 6.5–13.6) per 100,000 during 1990–2015.
Total DALYs from LRI decreased by 40.6%, from 20,746,747 (95% UI 17,954,899–23,444,142) in 1990 to 11,098,243 (95% UI 9,857,095–12,396,566) in 2015. LRI, which was the leading cause of DALYs in 1990, was ranked fourth in 2015, behind ischemic heart disease, neonatal preterm birth complications, and neonatal encephalopathy. LRI DALY rates were 5594 (95% UI 4851–6334) and 1712 (95% UI 1520–1912) DALYs per 100,000 population in 1990 and 2015, respectively, a 69.4% reduction. About 4.9% (95% UI 4.3–5.5) of DALYs in all ages and 12.2% (95% UI 10.8–13.8) of DALYs in children under 5 were due to LRI in 2015.
Age-standardized DALY rates were 3411 per 100,000 (95% UI 2,993–3,824) in 1990 compared to 1518 per 100,000 (95% UI 1357–1673) in 2015 in the EMR. Global age-standardized DALY rates for LRI were lower than those in the EMR: 3310 (95% UI 3033–3551) in 1990, and 1428 (95% UI 1330–1511) in 2013. There was a 56.9% reduction in age-standardized DALY rates at the global level, which was similar to the EMR (55.5% reduction) during 1990–2015. Figure 3 presents trends in age-standardized and all-ages LRI DALY rates between 1990 and 2015 globally and for the EMR.
Figure 4 shows age-standardized LRI DALY rates in the EMR countries. The highest rates were seen in Somalia, Afghanistan, and Djibouti. LRI DALY rates did not differ significantly between males and females.
Figure 5 shows DALY rates for different etiologies of LRI in EMR countries in 2015. The largest variation in country-specific DALYs (highest to lowest ratio) was observed for Hib (2068.7) compared to 125.5 for pneumococcus, 109.4 for RSV, and 30.6 for influenza. The DALY rate for Hib was less than one DALY per 100,000 in UAE and Qatar, compared to 916.7 in Somalia and 458.5 in Afghanistan (Fig. 5).
Figure 6 shows the LRI DALY rates attributable to different risk factors in 2015. Childhood undernutrition, household air pollution from solid fuels, ambient particulate matter pollution, suboptimal breastfeeding, secondhand smoke, no handwashing with soap, and zinc deficiency were the most important risk factors for LRI in children under 5. Among those aged 70 years or older, ambient particulate matter pollution, household air pollution from solid fuels, smoking, no handwashing with soap, secondhand smoke, and alcohol use were the main risk factors.
LRI is one of the leading causes of morbidity and mortality in the EMR. Efforts are urgently needed to prevent and control LRI in the region, especially in the low-income countries of the region. All countries should consider adopting vaccines against pneumococcus, if they have not already, to reduce the burden. To adequately address the LRI burden, a public health and health care systems approach is needed. A comprehensive plan that includes addressing known risk factors such as poor diet, smoking, and exposure to secondhand smoke; health systems to improve prevention and treatment of cases; and community programs to increase awareness and immunization uptake are needed. A reliable surveillance system is required to monitor trends of disease burden and evaluate new interventions.
Unstable economies, political instability, and unrest in the region are major barriers to improving health. Therefore, it is important for the international community to work to improve political stability in the EMR, and to strengthen support for low-income countries and disadvantaged groups, in order to reduce LRI morbidity and mortality in the region.