Abstract

1. Introduction

Pneumonia is the most common illness affecting infants and children globally. It is the most common cause of under-5 (U-5) mortality and contributes to 15% of U-5 mortality in 2017, killing an estimated 808,920 children [1]. World Health Organization (WHO) data indicate that acute respiratory infections (ARIs) are the second most common cause of disability-adjusted life years lost around the world [1]. During the Millennium Development Goal era from 2000 to 2015, the WHO-led ARI control program reduced the burden of pneumonia deaths from 1.7 million annual cases to 0.9 million, a 30% decrease in burden [2]. During the same time, the pneumonia mortality rate decreased by nearly 51% [3,4].

The ARI control program is dependent on the early identification and treatment of children with signs and symptoms suggestive of pneumonia, presuming a bacterial etiology. The WHO and United Nations Children’s Fund (UNICEF), in 2013, published the integrated Global Action Plan for Pneumonia and Diarrhea (GAPPD), which outlined a framework for ending preventable child deaths due to diarrhea and pneumonia by 2025 [2]. The GAPPD emphasizes a “protect, prevent, treat” approach and includes proven effective interventions [2]. However, estimates suggest that the sustainable development goal to eliminate preventable child deaths by 2030 will remain improbable unless deaths due to childhood pneumonia are significantly reduced [5].

However, more knowledge on the risk factors affecting the severity of pneumonia is required to reduce deaths from childhood pneumonia. Studies from low/middle-income countries (LMICs) have tried to identify the risk factors for severe pneumonia [6,7,8,9,10,11,12,13,14,15,16,17], but only a few studies from India have reported the risk factors for severe pneumonia [6,8,13]. More clinical studies from India are needed as the country alone contributes to 32% of the annual global burden of pediatric pneumonia [18]. India had the highest number of global U-5 deaths due to pneumonia with an estimated 508 deaths per day in 2017 [18]. No clinical study on the risk factors for child pneumonia has been published from the state of Madhya Pradesh (MP), India. Since MP has one of the highest infant and childhood mortalities in India [19], the present study has been undertaken to fill the evidence gap on the risk factors for severe child pneumonia. The aim of this study is to develop recommendations for appropriate interventions to address the demographic, socioeconomic, and environmental risk factors for severe pneumonia in children in the age range of 1–59 months in Ujjain, MP, India.

2. Materials and Methods

3. Results

During the study period, 270 children with pneumonia (60% boys and 40% girls), with the mean [±standard deviation (SD)] age of 18.5 (± 17.5) months were enrolled. Figure 1 provides the flow chart of the patient recruitment process. Considering the 270 children, 172 children were diagnosed with severe pneumonia, and the remaining 98 children had pneumonia according to the WHO classification. The prevalence of severe pneumonia was, thus, 63.7% (95% CI 57.9–69.4). The signs and symptoms at the time of admission are shown in Table 1.

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Figure 1

Flow chart of the patient recruitment process. WHO- World Health Organization, IV-Intravenous, IM-Intramuscular, HIV-Human Immunodeficiency Virus, AIDS-Acquired Immunodeficiency Syndrome.

The mean (±SD) duration of signs and symptoms before admission was 4 (±2.1) days. A total of 38 (14%) children required ventilatory support for a mean (±SD) duration of 36 (±5) h. Complicated pneumonia was diagnosed in 17 (6%) children, and 16 (6%) children died during the hospital stay.

4. Discussion

The present study included children with WHO-defined symptoms and other signs to define pneumonia and severe pneumonia [2]. The other included signs which were part of the initial assessment, and whose values were ascertained by other studies, were cyanosis, toxic look, severe pallor (Hb<7 gm/dL), severe dehydration, shock, and meningeal irritation [28,29,30].

During our study, severe pneumonia was more common in children between two and 12 months of age compared with children between 13 and 60 months of age. The global prevalence of pneumonia is highest in the age group of 1–4 years [18]. Children residing in rural areas were more affected with severe pneumonia compared with children living in urban areas, and the condition showed a marked male predilection. Similar findings have been reported in other regions of India and other neighboring countries like Bhutan and Nepal [31,32].

The present study reported that prematurely born children had an increased risk of severe pneumonia. Similar results were reported in another community-based study [33]. The underlying reason could be the effects of premature birth, such as poor infant feeding, and the resultant failure of childhood growth. A decrease in growth failure indices such as stunting and wasting can bring about a significant decrease in pneumonia mortality [18]. Pneumonia developed in 4–9.6% of children with post-measles infection, depending on whether they received antibiotic treatment [34]. This cause of pneumonia, thus, can be prevented by prioritization of measles vaccination along with pneumococcal conjugate vaccine (PCV) and haemophilus influenzae type B (HIB) vaccine. PCV was not introduced in the duration of the study; however, the HIB vaccine was given as part of the pentavalent vaccine. During the present study, the children that did not receive vaccines covered in the expanded program of immunization had an increased risk of severe pneumonia. Respiratory infections were less common among children who were completely immunized than in children with incomplete immunization [18]. The increased global HIB vaccination between 1990 and 2017 reduced the U-5 mortality by 11.4%, which is the maximum among all known interventions [18]. Children having congenital heart disease (CHD) had an increased risk of severe pneumonia in our study. A left-to-right shunt is expected to have an increased risk of pneumonia and heart failure. A Nigerian study, which included 121 children with pneumonia, reported 14 (11.5%) having a CHD [35]. Children who received any home treatment had an increased risk of severe pneumonia in the present study. This could be due to greater prescription of antibiotics in the study area [36,37]. Treatment with inappropriate antibiotics could have increased the risk of severe pneumonia.

Among the environmental risk factors, children living in kuccha houses had an increased risk of severe pneumonia. Kuccha houses are typically built by the poor and is a recognized risk factor for pneumonia in other Asian countries as well [31,32]. Overcrowding and poorly ventilated living areas were identified as risk factors for severe pneumonia. Higher levels of outdoor pollution in urban areas [18,38], high levels of solid fuel use causing indoor pollution in rural areas, and poorly constructed houses were the main reasons for the increased risk of pneumonia in children in our study [18,39]. LMICs that implemented measures to decrease exposure to household air pollution reduced pneumonia mortality by around 8%, but increased exposure to ambient air pollution increased mortality by around 4% [18]. Although open air defecation is not directly related to childhood pneumonia, it may be a common risk factor for both diarrhea and pneumonia as proposed by the WHO [2].

The present study evaluated host biomarkers like theTLC count, which was useful only in the presence of moderate leukocytosis. Generally, like the conclusion in other studies, it can be concluded that TLC and neutrophil percentage were not useful in distinguishing pneumonia from severe disease [40]. However, a CRP cut-off of 20 mg/L had a high specificity (90%) and positive predictive value (92%) to distinguish non-severe from severe disease. Thus, a CRP more than 20 mg/L might have some utility in predicting severe pneumonia in our and similar settings.

A primary limitation of this study was that the study did not ascertain the etiology of pneumonia in children, because it was not the primary study objective. Other limitations included the absence of blood investigations of the children due to the non-specific nature of the leukocyte count and C-reactive proteins in distinguishing pneumonia from severe pneumonia and the non-presentation of antibiotic use data as all children were managed using standard IndiaCLEN treatment guidelines. Another limitation of the study is the data are from a single teaching hospital. The results are generalizable to similar resource-limited settings, but hospital-to-hospital variations are expected.

5. Conclusions

Childhood pneumonia has been identified as the major “forgotten killer of children” by UNICEF and the WHO. Multiple modifiable risk factors for severe pneumonia have been identified in this study. Pediatricians and other health care workers, including the grassroot health workers, should be aware of these risk factors of severe pneumonia when managing the patient with pneumonia. The management of the modifiable risk factors may reduce mortality due to severe pneumonia.

Acknowledgments

Supplementary Materials

The following are available online at https://www.mdpi.com/1660-4601/17/13/4637/s1, Table S1: title-Definitions used in the study.

Appendix A

(A). Basic Demographic Information

1. Enrolment number ______________________

2. Date of the form filling _____________________

3. Name ______________ Surname ___________

4. Date of birth ____________________

5. Age in months ________________

6. Sex       Male       Female

7. IPD number

8. Date of admission

9. Date of discharge/death

10. Residence       Rural        Urban

(B). Signs and symptoms at presentation in hospitalized children with severe pneumonia

Signs/symptoms	Yes	No
Fast breathing
Chest indrawing/difficulty in breathing
Not able to drink
Persistent vomiting
Convulsions
Lethargic/Unconscious
Stridor in a calm child
Severe acute malnutrition
Cyanosis
Toxic look
Severe pallor (Hb<7 gm/dL)
Severe dehydration
Shock
Meningeal irritation
Crepitations
Fever [Low grade fever (37 °C–38 °C) High grade fever (>38 °C)]
Diarrhea
Significant lymphadenopathy
Running nose
Wheeze
Ear discharge

(C). Socio-demographic and birth related co-variates

	Check Box
Born premature
No
Yes
Born term low birth weight
No
Yes
Mother’s education
Illiterate
Up-to secondary
Graduate
Mother’s occupation
Working
Nonworking

(D). Past history related co-variates with severe pneumonia

	Check Box
Exclusive breastfeeding (till 6 months of age)
Yes
No
Vitamin A supplementation
Given
Not given
Measles
No
Yes
Incomplete vaccination
No
Yes
Kerosene ingestion
No
Yes
Antibiotic treatment
No
Yes
Hospitalization
No
Yes
Acyanotic congenital heart disease
Absent
Present
Home treatment tried (other than self-medication)
Yes
No

(E). Environmental covariates

Type of family	Check Box
Nuclear
Joint
Number of family members
Upto 5
5–10
>10
Type of home
Pukka
Kuccha
Overcrowding
No
Yes
Indoor air pollution
No
Yes
Poor ventilation in living area
No
Yes
Contact with TB
No
Yes
Smoking at home
No
Yes
Drinking water source
Underground water
Tap water
Open defecation
No
Yes

(F). Investigation:

(G). Anthropometry

Author Contributions

S.K.K., M.D., A.M. and A.P. participated inthe conception and design of the study. S.K.K. and A.M. collected the data. A.M. and A.P. did data management. A.P. supervised the data collection. S.K.K., A.M. and A.P. performed the statistical analysis. S.K.K. and A.P. drafted the manuscript. S.K.K., A.M, M.D., and A.P. revised the paper critically for substantial intellectual content. All authors have read and agreed to the published version of the manuscript.

Funding

This study is funded by Uppsala Universitet’s L R Åkerhams post-doctoral scholarship in clinical research, obtained by Ashish Pathak. The funders had no role in study design, data collection, data analysis, decision to publish, or preparation of the manuscript.

Conflicts of Interest

The authors declare no conflict of interest.

References