Abstract
Introduction:
Over 2 million children die from pneumonia each year accounting for almost one in five children’s deaths worldwide which is estimated to be 18% of mortality cases. Therefore, this study is aimed to assess treatment outcome and its determinant factors among under-five patients, Jimma, Ethiopia.
Methods:
Study design was conducted on 522 under-five children with severe pneumonia from 1 January 2017 to 30 December 2020. Pretested chart review format was used to collect data. Data were entered into EpiData, version 3.1, and exported to Statistical Package for the Social Sciences, version 23, for analysis. Logistic regression analysis with 95% confidence interval was used to declare statistical significance at p value <0.05.
Results:
Among 522 under-five children with severe pneumonia, majority (83.91%) of them were improved, whereas 1 over 6 (16.09%) of them were died. This finding showed that children who have malnutrition (adjusted odds ratio = 7.23 (3.17–14.51), p = 0.000), positive serostatus for HIV (adjusted odds ratio = 5.01 (1.91–12.13), p = 0.001), history of upper respiratory tract infections (adjusted odds ratio = 3.27 (1.55–6.91), p = 0.002), unvaccinated (adjusted odds ratio = 4.35 (1.60–11.79), p = 0.004), having complicated types of pneumonia (adjusted odds ratio = 8.48 (4.22–16.65), p < 0.001), and comorbidity disease (adjusted odds ratio = 5.21 (2.03–13.3), p < 0.001) were statistically significant with mortality.
Conclusion:
This study showed that mortality secondary to severe pneumonia was high. Being malnourished, positive serostatus for HIV infection, history of upper respiratory tract infections, unvaccinated, having complicated type of pneumonia, and other comorbidity disease were identified as determinant factors of mortality. Committed, harmonized, and integrated intervention needs to be taken to reduce mortality from severe pneumonia by enhancing child’s nutrition status, early detection and treatment, effectively vaccinating children, and preventing other comorbidity diseases.
Keywords: Pneumonia, child, Ethiopia, mortality, treatment, outcome
Introduction
Globally, pneumonia is the leading cause of child mortality from infectious diseases, accounting for approximately 16% of the 5.6 million under-five deaths, killing around 900,000 children in 2016.1,2 This revenues a loss of 2500 children’s lives every day or over 100 every hour. “The forgotten child killer”: Pneumonia kills two under-five kids every minute. Pneumonia kills nearly 1 million children under the age of five around the world, causing more deaths than HIV/AIDS, and diarrhea and malaria combined. 3
According to the World Health Organization (WHO) approximations, there are 156 million cases of pneumonia each year in under-five children, with as many as 20 million cases severe enough to require hospital admission and 1.2 million deaths annually.4,5 More than 90% of all deaths due to pneumonia in children aged less than 5 years take place in 40 countries. The incidence and severity of childhood pneumonia was highest in Africa and South East Asia, which accounted for 30% and 39%, respectively, of the global burden of severe cases. In these two regions, 15 countries accounted for two-thirds of all childhood pneumonia episodes and severe cases.5,6
The African region has, in general, the highest burden of global child mortality—50% of worldwide deaths from pneumonia in this age group. More than 490,000 under-five children died by pneumonia in 2016 in Sub-Saharan Africa. 7 In contrast, less than 2% of these deaths take place in the European region and less than 3% in the region of the Americas. 3 Pneumonia continues to be the major cause of death in children. In Ethiopia, pneumonia is a primary particular infection killing under-five children. It is estimated that in Ethiopia, 3.37 million children encounter pneumonia annually which contributes to 18% of mortality of children and killing over 40,000 under-five children every year. 5
Burden and severity of childhood pneumonia is high in Ethiopia children due to limited coverage and affordability of effective preventive interventions like immunization of pneumococcal conjugate vaccine, respiratory syncytial virus, and lack of worthy access to health care and unavailability of effective management strategies. The huge discrepancy between the current incompatibly big and high peal of pneumonia reflects poorly designed prevention strategies in the poorest settings like Ethiopia.8,9 It is therefore important to look at a combination of strategies for reducing the morbidity and mortality from pneumonia. So, addressing current gaps for prevention of mortality of under-five pneumonia is critical to achieving Sustainable Development Goal (SDG 3). 10
The widespread nature of the problem in Ethiopia has already killed thousands of children which need to look for lasting solution to end the problem. Despite the sustained effort to stop the problem, pneumonia continues to be common cause of mortality of children which calls for innovative strategies that will come about only through systematic researches. Data on the outcome of severe pneumonia and their related risk factors are important for planning child health care services but scarce in Ethiopia. Therefore, this study aimed to assess outcome of severe pneumonia and its determinant factors.
Materials and methods
A retrospective study design was conducted on 522 under-five severe pneumonia cases from 1 to 30 March 2021 at Jimma University Medical Center (JUMC), Ethiopia. The sample size was calculated by EPI info sample size calculations by taking 95% confidence level, power 80%, percent outcome in unexposed group 22%, percent outcome in exposed group 33.42%, and odds ratio 1.79, 11 which brings initial sample size 474, and by considering 10% incomplete medical records, the final sample size was 522. All eligible cases were included in the study. Discharge log book was used to identify cases admitted from 1 January 2017 to 30 December 2020. All medical records with diagnosis of severe pneumonia, age from 2 to 59 months, were included in the study. Data were collected from medical records using the pretested structured chart review format. The chart review format was adapted after reviewing relevant literatures, 11 - 14 and it contains two parts. Part 1 is about the socio-demographic characteristics like child age, sex, residency, and housing condition of the family. Part 2 is about preexisting medical or comorbid condition characteristics of under-five children, such as nutritional status, serostatus for HIV, immunization status, and previous history of disease. The tool was checked for content and construct validity by two medical doctors from JUMC and two pediatric Master of Science (MSc) instructors from school of nursing, Jimma University. Reliability test was done, and Cronbach’s alpha coefficient was 0.87. Data were collected by two trained Bachelor of Science (BSc) degree holder nurses. The principal investigator supervised and checked the completeness and quality of data on daily basis. The incomplete medical records and medical records without full information were excluded from the study.
Statistical analysis
Data were coded and entered into EpiData, version 3.1, and exported to IBM Statistical Package for the Social Sciences (SPSS) Statistics for Windows, version 23.0 (IBM Corp., Armonk, NY, USA). Descriptive statistics were used to describe the socio-demographic characteristics and preexisting medical or comorbid conditions of under-five children. Then, all independent variables were first tested by bivariable logistic regression and variables with p value ⩽0.25 were further considered for multivariable logistic regression to control confounding variables. Finally, the p value <0.05 at 95% confidence interval (CI) was declared a statistically significant.
Severe pneumonia
Severe pneumonia is characterized by cough or difficult breathing plus at least one of the following: central cyanosis, hypoxemia (sustained oxygen saturation <90% in room air at sea level), temperature ⩾38.5°C (101.3°F), capillary refill ⩾2 s, inability to breastfeed or drink, vomiting everything, convulsions, lethargy or unconsciousness, and moderate to severe respiratory distress. 15
Complicated pneumonia
Complicated pneumonia is characterized by combination of pneumonia with local complications (e.g. parapneumonic effusion, empyema, necrotizing pneumonia, and lung abscess) and systemic complications (e.g. bacteremia, metastatic infection, multiorgan failure, acute respiratory distress syndrome, and disseminated intravascular coagulation). 16
Malnutrition
The weight-for-height ratio of less than minus 2 standard deviations below the median WHO growth standards or weight-for-height ratio of below 80% of the median or presence of nutritional edema. 17
Ethical approval
Ethical approval for this study was obtained from Research Ethics Committee of School of Nursing, Jimma University [Nurs/90/2021]. Then the letter was submitted to JUMC administration to get permission prior actual data collection. Written informed consent was taken from Ethics Committee of JUMC prior to study initiation. The information gathered from medical records was confidential, secured, and used for research purposes only.
Results
Socio-demographic characteristics
Among the 522 cases analyzed, around half (48.7%) of them were found between 2 and 12 months of age and 64% of them were female (see Table 1).
Table 1.
Socio-demographic characteristics of under-five children admitted with severe pneumonia.
| S. No. | Variable | Frequency | % | |
|---|---|---|---|---|
| 1. | Age (months) | 2–12 | 254 | 48.7 |
| 13–36 | 214 | 41.0 | ||
| 37–59 | 54 | 10.3 | ||
| 2. | Sex | Male | 236 | 45.2 |
| Female | 286 | 54.8 | ||
| 3. | Residency | Urban | 188 | 36.0 |
| Rural | 334 | 64.0 | ||
| 4. | Number of windows in house | Up to three | 308 | 58.6 |
| Greater than four | 214 | 41.4 | ||
| 5. | Kitchen | Separated from house | 188 | 36.0 |
| Not separated from house | 334 | 64.0 | ||
| 6. | Smoker in house | Yes | 188 | 36.0 |
| No | 334 | 64.0 | ||
Preexisting medical conditions, comorbidity, and treatment outcome
Out of total sample, more than one-third, 204 (39.1%), of the cases had malnutrition and 171 (32.8%) of them were not vaccinated. Among 522 children admitted with severe pneumonia, 136 (26.1%) of them had complicated severe pneumonia and 260 (48.2%) children had other comorbidity disease. From total under-five children admitted by severe pneumonia, 84 (16.1%) of them were died and 438 (83.9%) were improved (see Table 2).
Table 2.
Preexisting medical conditions and treatment outcome of under-five children admitted with severe pneumonia.
| S. No. | Variable | Frequency | % | |
|---|---|---|---|---|
| 1. | Duration illness prior to admission | Up to 3 days | 214 | 41.0 |
| 4 to 7 days | 210 | 40.2 | ||
| More than 8 days | 98 | 18.8 | ||
| 2. | Nutritional status | Malnutrition | 204 | 39.1 |
| Non-malnutrition | 318 | 60.9 | ||
| 3. | Serostatus for HIV | Reactive | 49 | 9.4 |
| Non-reactive | 473 | 90.6 | ||
| 4. | Previous history of URTI | Yes | 182 | 34.9 |
| No | 340 | 65.1 | ||
| 5. | Previous history of measles | Yes | 28 | 5.4 |
| No | 494 | 94.6 | ||
| 6. | Immunization status | Fully vaccinated | 162 | 31.0 |
| Vaccinated for age | 128 | 24.5 | ||
| Partially vaccinated | 61 | 11.7 | ||
| Not vaccinated | 171 | 32.8 | ||
| 7. | Types of pneumonia | Non-complicated | 386 | 73.9 |
| Complicated | 136 | 26.1 | ||
| 8. | Comorbidity | Yes | 260 | 49.8 |
| No | 262 | 50.2 | ||
| 9. | Outcome | Improved | 438 | 83.9 |
| Died | 84 | 16.1 | ||
URTI: upper respiratory tract infection.
Determinant factors associated with treatment outcome of severe pneumonia
All study variables were tested by binary logistic regression analysis and variable those had less than 0.25 p-values were candidate for the multivariate logistic regression to control confounding variable and to determine potential predictors of outcome of severe pneumonia.
On multivariable logistic regression, six variables were found to have significant association with mortality of severe pneumonia. This finding showed that children who had malnutrition (adjusted odds ratio (AOR) = 7.23 (3.17–14.51), p = 0.000), children who were positive serostatus for HIV (AOR = 5.01 (1.91–12.13), p = 0.001), children who had previous history of upper respiratory tract infection (URTI; AOR = 3.27 (1.55–6.91), p = 0.002), children who were not vaccinated (AOR = 4.35 (1.60–11.79), p = 0.004), children who had complicated types of pneumonia (AOR = 8.48 (4.22–16.65), p < 0.000), and children who had comorbid disease with severe pneumonia (AOR = 5.21 (2.03–13.3), p < 0.001) were significantly associated with mortality from severe pneumonia among under-five children (see Tables 3 and 4).
Table 3.
Binary logistic regression analysis of determinant factors associated with treatment outcome of severe pneumonia.
| Variable | Outcome of severe pneumonia | COR | p value | ||
|---|---|---|---|---|---|
| Improved | Died | ||||
| Kitchen | Separated from house | 174 | 14 | 1 | |
| Not separated from house | 264 | 70 | 3.29 (1.80–6.03) | 0.00 | |
| Smoker in house | Yes | 110 | 40 | 2.71 (1.67–4.37) | 0.00 |
| No | 328 | 44 | 1 | ||
| Duration illness prior to admission | Up to 3 days | 172 | 42 | 1 | |
| 4 to 7 days | 192 | 18 | 0.38 (0.21–0.69) | 0.01 | |
| More than 8 days | 74 | 24 | 1.32 (0.75–2.35) | 0.33 | |
| Nutritional status | Malnutrition | 132 | 72 | 13.9 (7.30–26.49) | 0.00 |
| Non-malnutrition | 306 | 12 | 1 | ||
| Serostatus for HIV | Reactive | 26 | 23 | 5.97 (3.20–11.13) | 0.00 |
| Non-reactive | 412 | 61 | 1 | ||
| Previous history of upper respiratory tract infection | Yes | 123 | 69 | 6.04 (3.62–10.08) | 0.00 |
| No | 315 | 25 | 1 | ||
| Previous history of measles | Yes | 12 | 16 | 8.30 (3.78–18.42) | 0.00 |
| No | 426 | 68 | 1 | ||
| Immunization status | Fully vaccinated | 154 | 8 | 1 | |
| Vaccinated for age | 118 | 10 | 1.63 (0.62–4.26) | 0.31 | |
| Partially vaccinated | 51 | 10 | 3.77 (1.41–10.07) | 0.008 | |
| Not vaccinated | 115 | 56 | 9.37 (4.30–20.43) | 0.00 | |
| Types of pneumonia | Non-complicated | 359 | 27 | 1 | |
| Complicated | 79 | 57 | 7.59 (5.71–16.11) | 0.00 | |
| Comorbidity | Yes | 186 | 74 | 10.02 (5.04–19.9) | 0.00 |
| No | 252 | 10 | 1 | ||
COR: crude odds ratio.
Table 4.
Determinant factors associated with treatment outcome of severe pneumonia.
| Variable | Outcome of severe pneumonia | COR | AOR | p value | ||
|---|---|---|---|---|---|---|
| Improved | Died | |||||
| Nutritional status | Malnutrition | 132 | 72 | 13.9 | 7.23 (3.17–14.51) | 0.000 |
| Non-malnutrition | 306 | 12 | 1 | |||
| Serostatus for HIV | Reactive | 26 | 23 | 5.79 | 5.01 (1.91–12.13) | 0.001 |
| Non-reactive | 412 | 61 | 1 | |||
| Previous history of URTI | Yes | 123 | 59 | 6.04 | 3.27 (1.55–6.91) | 0.002 |
| No | 315 | 25 | 1 | |||
| Immunization status | Fully vaccinated | 154 | 8 | 1 | ||
| Vaccinated for age | 118 | 10 | 1.63 | 2.11 (0.59–7.48) | 0.245 | |
| Partially vaccinated | 51 | 10 | 3.77 | 3.03 (0.88–10.40) | 0.078 | |
| Not vaccinated | 115 | 56 | 9.37 | 4.35 (1.60–11.79) | 0.004 | |
| Types of pneumonia | Non-complicated | 359 | 27 | 1 | ||
| Complicated | 79 | 57 | 7.59 | 8.48 (4.22–16.65) | 0.000 | |
| Comorbidity | Yes | 186 | 74 | 10.0 | 5.21 (2.03–13.3) | 0.001 |
| No | 252 | 10 | 1 | |||
COR: cured odds ratio; AOR: adjusted odds ratio; URTI: upper respiratory tract infection.
Discussion
This study showed that among 522 under-five severe pneumonia, 4 out of 25 (16.09%) were died. This finding is nearly similar with the estimation of the under-five pneumonia death (18%) of the Ethiopia. 2 However, mortality rate in this study is higher than studies conducted in the Philippines, 4.7%; 13 India, 10.5%; 18 and China, 12%. 19 This may be due to the study setting, quality of health care system, and deference of socio-demographic factors. This study showed that children who had malnutrition were seven times more likely to die by severe pneumonia than children who had no malnutrition. This finding is consistent with the study conducted in the Philippines, 13 Brazil, 20 and Tanzania, 21 which indicates that malnutrition is significantly associated with the mortality of severe pneumonia. This may be due to the fact that malnutrition weakens a child’s overall immune system, as an adequate amount of protein and energy is needed for proper immune system functioning. In addition, undernourished children have weakened respiratory muscles, which inhibit them from adequately clearing secretions in their respiratory tract. 22
This result showed that children with positive serostatus for HIV were five times more risk to die by severe pneumonia than children who were negative serostatus for the HIV. This finding is similar to a study conducted in Tanzania which shows HIV infection is one of the predictors of the severe pneumonia treatment failure. 21 This is because HIV infection weakens the immune system which leads the children to serious or life-threatening and increases the mortality of severe pneumonia.
This study finding revealed that children who have previous history of URTI were three times more likely to die by severe pneumonia than children who have no previous history of URTI. Similarly, the study conducted in the Philippines 13 showed that the previous history of URTI is significantly associated with death of under-five severe pneumonia. Available evidence showed that an increased risk of pneumonia or acute lower respiratory tract infections in children who have had a prior episode of pneumonia or wheezing, and viral infections, particularly with respiratory syncytial virus or influenza virus, also predisposes to invasive pneumococcal disease for a period of 4 weeks.23,24
According to this result, children who were not vaccinated were fourfold more risk of dying due to severe pneumonia than children who were fully vaccinated. This is similar to a study conducted in India which showed that use of conjugate vaccines against pneumonia, particularly Streptococcus pneumonia and Haemophilus influenzae, appears to be justified for the prevention of pneumonia morbidity and mortality in children younger than 5 years. 18 Immunization also helps to reduce childhood pneumonia in two ways. First, vaccinations help prevent children from developing infections that directly cause pneumonia, such as Haemophilus influenzae type b (Hib). Second, immunizations may prevent infections that can indicate pneumonia as a complication like measles and pertussis. 25
The findings of the study indicated that children who have complicated types of pneumonia are threefold more likely to die by severe pneumonia than children who have non-complicated types of pneumonia. Similarly, study conducted in Bangladesh revealed that complicated types of pneumonia increased risk of pneumonia mortality. 26 This might be due to complicated types of pneumonia being able to worsen preexisting chronic conditions, particularly those of the heart and lungs which increase the mortality.
This study revealed that children who have comorbidity disease with severe pneumonia were also four times more risky to die by severe pneumonia than children who have no comorbidity disease with severe pneumonia. This is consistent with a study conducted in China 19 and Bangladesh, 26 which showed that septic shock, multiorgan dysfunction, acute renal failure, liver dysfunction, decreased hemoglobin, and albumin levels are associated with mortality of severe pneumonia. This could be due to other comorbidity disease increased risk for having a serious or life-threatening and increase the mortality of severe pneumonia. Although this finding revealed important detection, it is not free of limitation. One limitation of this study is being a retrospective study design which does not include environmental and health professional factors. Therefore, prospective longitudinal study is recommended to include all determinant factors that result in death of under-five patients diagnosed with severe pneumonia.
Conclusion
This study showed that mortality secondary to severe pneumonia was high. Being malnourished, positive serostatus for HIV infection, previous history of URTI, not vaccinated, having complicated type of pneumonia, and other comorbidity disease were identified as determinant factors of mortality. Committed, harmonized, and integrated intervention needs to be taken to reduce mortality from severe pneumonia by enhancing child’s nutrition status, early detection and treatment, effectively vaccinating children, and preventing other comorbidity diseases.
Acknowledgments
We would like to extend our thanks to Jimma University Medical Center for their cooperation during data collection and data collectors.
Footnotes
Author contributions: All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising, or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.
Ethical approval: Ethical approval for this study was obtained from Research Ethics Committee of School of Nursing, Jimma University [Nurs/90/2021]. Then the letter was submitted to Jimma University Medical Center (JUMC) administration to get permission prior actual data collection. The information gathered from medical records was confidential and used for research purposes only.
Informed consent: Written informed consent was taken from Ethics Committee of Jimma University Medical Center prior to study initiation. The information gathered from medical records was confidential, secured, and used for research purposes only.
ORCID iDs: Kenenisa Tegenu 
https://orcid.org/0000-0001-7173-3242
Ebissa Bayana
https://orcid.org/0000-0001-5611-6799
References
- 1. UNICEF. Monitoring the situation of children multiple indicator cluster surveys (MICS) child health/pneumonia, 2017, https://www.unicef.org/eap/sites/unicef.org
- 2. Pires SM, Fischer-Walker CL, Lanata CF, et al. Aetiology-specific estimates of the global and regional incidence and mortality of diarrhoeal diseases commonly transmitted through food. PLoS ONE 2015; 10(12): e0142927. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. UNICEF data. UNICEF data: monitoring the situation of children and women, 2020, https://data.unicef.org/
- 4. Rudan I, Boschi-Pinto C, Biloglav Z, et al. Epidemiology and etiology of childhood pneumonia. Bull World Health Org 2010; 86(5): 408–416B. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Walker CLF, Rudan I, Liu L, et al. Global burden of childhood pneumonia and diarrhoea. Lancet 2013; 381(9875): 1405–1416. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Nair H, Simões EA, Rudan I, et al. Global and regional burden of hospital admissions for severe acute lower respiratory infections in young children in 2010: a systematic analysis. Lancet 2013; 381(9875): 1380–1390. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. UNICEF. The state of the world’s children 2016: a fair chance for every child. New York: UNICEF, 2016, https://www.unicef.org/reports/state-worlds-children-2016
- 8. Zar HJ. Childhood pneumonia—looking beyond mortality. African J Respir Med 2016; 11(2): 12–14. [Google Scholar]
- 9. WHO and UNICEF. Pneumonia and diarrhea: tackling the deadliest diseases for the world’s poorest children. UNICEF/WHO, June 2012, https://data.unicef.org/ [DOI] [PubMed]
- 10. UNICEF. Integrated Global Action Plan for the Prevention and Control of Pneumonia and Diarrhoea (GAPPD). WHO/UNICEF, 2015, https://www.who.int/publications/i/item
- 11. Jroundi I, Mahraoui C, Benmessaoud R, et al. Risk factors for a poor outcome among children admitted with clinically severe pneumonia to a university hospital in Rabat, Morocco. Int J Infect Dis 2014; 28: 164–170. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. Karim Eldin MA, Salih AS, El Fatih ZE, et al. Characteristics associated with severe pneumonia in under-five children admitted to emergency units of two teaching hospitals in Khartoum, Sudan. Sudan J Paediatr 2011; 11(2): 25–31. [PMC free article] [PubMed] [Google Scholar]
- 13. Dembele BPP, Kamigaki T, Dapat C, et al. Aetiology and risks factors associated with the fatal outcomes of childhood pneumonia among hospitalised children in the Philippines from 2008 to 2016: a case series study. BMJ Open 2019; 9(3): e026895. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14. Derek J, Williams YZ, Carlos G, et al. Predicting severe pneumonia outcomes in children. Pediatrics 2019; 138(4): e20161019. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. Bradley JS, Byington CL, Shah SS. The management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis 2011; 53: e25–e76. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16. De Benedictis FMKE, Chang AB, Colin AA, et al. Complicated pneumonia in children. Lancet 2020; 396: 786–798. [DOI] [PubMed] [Google Scholar]
- 17. Training module course on the management of severe acute malnutrition, Federal Democratic Republic of Ethiopia, Ministry of Health. 2nd ed. Addis Ababa, Ethiopia: Republic of Ethiopia, Ministry of Health, 2013. [Google Scholar]
- 18. Farooqui H, Jit M, Heymann DL, et al. Burden of severe pneumonia, pneumococcal pneumonia and pneumonia deaths in Indian states: modelling based estimates. PLoS ONE 2015; 10(6): e0129191. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19. Shi T, Chen C, Huang L, et al. Risk factors for mortality from severe community-acquired pneumonia in hospitalized children transferred to the pediatric intensive care unit. Pediatr Neonatol 2020; 61(6): 577–583. [DOI] [PubMed] [Google Scholar]
- 20. Espinoza R, e Silva JRL, Bergmann A, et al. Factors associated with mortality in severe community-acquired pneumonia: a multicenter cohort study. J Crit Care 2019; 50: 82–86. [DOI] [PubMed] [Google Scholar]
- 21. Muro RP, Masoza TS, Kasanga G, et al. Predictors and outcome of first line treatment failure among under-five children with community acquired severe pneumonia at Bugando Medical Centre, Mwanza, Tanzania: a prospective cohort study. PLoS ONE 2020; 15(12): e0243636. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22. Wardlaw TM, Johansson EW, Matthew Hodge. Pneumonia the forgotten killer of children. Geneva: World Health Organization, 2016, https://apps.who.int/iris/handle/10665/43640 [Google Scholar]
- 23. Victora CG, Fuchs SC, Flores JAC, et al. Risk factors for pneumonia among children in a Brazilian metropolitan area. Pediatrics 1994; 93(6 Pt. 1): 977–985. [PubMed] [Google Scholar]
- 24. Kim PE, Musher DM, Glezen WP, et al. Association of invasive pneumococcal disease with season, atmospheric conditions, air pollution, and the isolation of respiratory viruses. Clin Infect Dis 1996; 22(1): 100–106. [DOI] [PubMed] [Google Scholar]
- 25. Tong N. Update on Background Paper, BP 6.22 Pneumonia, 2013, https://www.who.int/medicines/areas/priority_medicines/BP6_22Pneumo.pdf
- 26. Saha S, Hasan M, Kim L, et al. Epidemiology and risk factors for pneumonia severity and mortality in Bangladeshi children <5 years of age before 10-valent pneumococcal conjugate vaccine introduction. BMC Public Health 2016; 16(1): 1233. [DOI] [PMC free article] [PubMed] [Google Scholar]