Clinical and microbial spectrum of community-acquired pneumonia in children of north India

Abstract

We compared the clinical, radiological and microbial profile in children suffering from community-acquired pneumonia in rural populations of north India. A total of 125 such children were divided into two age groups of 2–12 months (Group A) and 13–60 months (Group B). After taking a history and clinical examination, routine investigations including full blood count, blood, urine, and nasopharyngeal swab culture and radiology were performed. Multiplex polymerase chain reaction for Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumoniae and Haemophilus influenzae was carried out. Failure to eat or drink was more common (40.9%) in Group A, than Group B (18.7%). Lung consolidation was more common in Group B. Blood and urine culture were found to be more positive in Group A while combined nasopharyngeal culture and multiplex polymerase chain reaction favoured more bacterial growth in Group B.

Keywords

Patients complete blood count multiplex polymerase chain reaction

Introduction

Pneumonia can be defined as ‘an acute inflammation of the pulmonary parenchyma caused by various infective and non-infective agents’.¹ Globally, pneumonia is recognised as a leading cause of under-five mortality.² According to the estimates of the World Health Organization (WHO), it accounts for almost 20% of overall childhood mortality.^3,4 The term ‘community-acquired pneumonia’ (CAP) refers to a lower respiratory tract infection occurring in a child who has not resided in a hospital or health care facility during the preceding 14 days.⁵

The diagnosis of CAP in children is mainly based on clinical symptoms. Tachypnoea is the most sensitive sign for predicting pneumonia in children, evident on chest radiography.⁶ In children over the age of one month, cough is the commonest symptom. Fever is common but not always present at the time of assessment. Fever alone occurring without cough or respiratory distress may still be due to pneumonia.⁷

Approximately one-third of cases of pneumonia in children have a viral aetiology.⁸ A wide spectrum of viruses, such as respiratory syncytial virus (RSV), rhinovirus, para-influenza types 1, 2, and 3 viruses, influenza A and B viruses, adenovirus, enteroviruses, coronaviruses and Epstein–Barr virus, have been identified in children. RSV infection is most often found in children <2 years of age.⁸ Some 60–70% of cases of pneumonia in children in India are bacterial.⁹ Between the ages of three months to three years, common pathogens include Streptococcus pneumoniae, Haemophilus influnenzae and Staphylococcus aureus. After this, they are S. pneumoniae and S. aureus. Gram-negative organisms cause pneumonia in early infancy, severe malnutrition and immune-compromised children.⁹

Radiologists understand that the role of imaging in CAP is for the confirmation or exclusion of pneumonia, differentiation between viral and bacterial causes, exclusion of other possible causes for the symptoms and the detection of related complications.¹⁰ Chest radiography is frequently performed in paediatric intensive care unit even in mild to moderate cases, although its appropriateness in children with CAP is still debatable, and current guidelines recommend its use only in order to verify the presence or absence of complication in severe cases.^11,12

The Paediatric Infectious Diseases Society and the Infectious Diseases Society of America national guidelines recommend that blood cultures should be obtained in children requiring admission for presumed bacterial CAP if it is moderate or severe, particularly in the latter.¹¹ This recommendation was intended to facilitate targeted antimicrobial therapy when an organism was isolated because culture-directed therapy is associated with improved outcome and reduces unnecessary broad-spectrum antimicrobial use.^13–15

Consequently, we sought to assess any difference in the clinical profile of CAP between infants and older children especially in rural populations which are always more vulnerable to progression to severe disease. Our study adds further details on disease spectrum and aetiology in different age groups; consequently better management may be pursued.

Methods

Our prospective cross-sectional study was conducted in the Department of Paediatrics and Department of Microbiology of the Uttar Pradesh University of Medical Sciences (UPUMS), Saifai, Etawah, UP from March 2016 to August 2017. Ethical clearance from our Institutional Ethical Committee was given. A total of 148 children from age group 2–60 months admitted consecutively in our department with complaints of fever, cough and difficulty in breathing were enrolled and 137 children diagnosed with CAP according to our definition (note 1 in Figure 1) were included after taking written and informed consent from parents or guardians.⁵ The revised WHO 2014 classification for pneumonia includes only two categories of pneumonia¹⁶

Pneumonia – fast breathing and/or chest indrawing.

Severe pneumonia – pneumonia with any general danger sign

Figure 1.

PCR products from mPCR shown on agarose gel. Lane 1 and 7, molecular weight markers (100 bp DNA ladder), lane 2 and 4 (S. pneumoniae), lane 3 (H. influenzae), lane 5 (C. pneumoniae) and lane 6 (negative control).

According to WHO, tachypnea is defined as

Respiratory rate >60/min for children <2 months of age,

Respiratory rate >50/min for children aged 2–12 months and

Respiratory rate >40/min for children aged 1–5 years.¹⁷

Patients with history of hospitalisation within two weeks, aspiration pneumonia, diagnosed as bronchiolitis or bronchial asthma by clinical or radiological basis and patients with congenital heart disease were excluded from the study.

Out of 137 CAP patients, 12 children did not complete the study for various reasons, leaving 125 patients. They were divided into two groups according to their age: Group A (93 patients) from 2 to 12 months and Group B from 13 to 60 months. A detailed history of presenting complaints, history of similar illness, immunisation status (note 2 in Figure 1), developmental milestones, nutrition and socio-economic status was taken.¹⁸ A full anthropometric, general and systemic examination was done. Respiratory rate was counted for a full minute after properly exposing the chest. Respiratory distress was assessed by examining respiratory rate, cyanosis, grunting, subcostal/intercostal retraction, nasal flaring, wheezing and or stridor. After examination, pneumonia was categorised according to WHO revised classification 2014 as either ‘Pneumonia’ or ‘Severe pneumonia’.¹⁶ Chest radiography was carried out on all patients and categorised as ‘normal’, ‘infiltrates’, ‘consolidation’ and ‘effusion’ according to WHO radiology working group standardised definitions for radiological pneumonia.¹⁹ Full blood count was measured using a fully automated analyser (Lablife D5 supreme). Norms of total leucocyte count (TLC) varied according to age (note 3 in Figure 1).²⁰

A blood culture sample was collected before administration of the first dose of antibiotics using sterile conditions in brain heart infusion broth, in the ratio of 10:1 (culture media:blood), 5 mL blood was inoculated in 50 ml blood culture bottle and sent to the microbiology laboratory within 2–3 h of collection.

For urine culture, 5 mL urine was collected in sterile conditions after appropriate part preparation (note 4 in Figure 1), sending it within 2–3 h of collection.

For nasopharyngeal culture, nasopharyngeal swabs were added to a vial of Skim Milk Glucose Glycerol Medium (HiMedia Laboratories Pvt Ltd, India), collected according to standard protocols.²¹ Samples were inoculated on appropriate media viz blood agar, MacConkey agar, chocolate agar and growth obtained after 24–48 h of aerobic incubation and identified by standard microbiological biochemical tests. For molecular detection of S. pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumoniae and H. influenzae, multiplex polymerase chain reaction (mPCR) was performed using specific primers (Table 1 and Figure 1).²² Treatment was pursued according to departmental protocols.

Table 1.

Primers for different organisms.

Organism (target gene)	Primer	Amplicon size (bp)
S. pneumoniae (lyt A)	F 5′-CGGACTACCGCCTTTATATCG-3′ R 5′-GTTTCAATCGTCAAGCCGTT-3′	229
M. pneumoniae (P1)	F 5′-ACTCGGAGGACAATGGTCAG-3′ R 5′-CAAACCCGGTCTTTTCGTTA-3′	483
C. pneumoniae (ompA)	F 5′-ACACGATGCAGAGTGGTTCA-3′ R 5′-TGTTTACAGAGAATTGCGATACG-3′	368
H. influenzae (16sRNA)	F 5′-TCCTAAGAAGAGCTCAGAGAT-3′ R 5′-TGATCCAACCGCAGGTTCC-3′	538

Results

There were 93 patients in Group A and 32 in Group B. The mean age in Groups A and B was 6.1 3.5 and 40.9 14.6 months, respectively. Other demographic data are shown in Table 2.

Table 2.

Demographic profile of study.

S. No.		Group A (2–12 months)	Group B (13–60 months)	Total
1.	No. of patients	93	32	125
2.	Mean age (months)	6.13 ± 3.48	40.94 ± 14.61	15.05 ± 17.22
3.	Male: female	2.44	1.29	2.05
4.	Weight (kg)	6.20 ± 1.73	12.49 ± 2.24	7.81 ± 3.33
5.	Complete immunisation^a	43.01%	28.13%	39.20%
6.	Exclusive breast feeding	31.25%	24.73%	23.07%

Children who received BCG, measles and three doses each of DPT and polio.

All patients presented with fever, cough and tachypnea. Consolidation was the most common finding in X-ray present in 64 (51.2%) patients. The rest of the clinical, radiological and TLC findings in both groups are given in Table 3.

Table 3.

Characteristic findings of CAP in children.

Findings	Characteristic	Group A (n = 93)		Group B (n = 32)		Total		p value
Findings	Characteristic	N	%	N	%	N	%	p value
Clinical features	Fever	93	100	32	100	125	100	N/A
	Cough	93	100	32	100	125	100	N/A
	Tachypnea	93	100	32	100	125	100	N/A
	Failure to eat/Drink	38	40.9	6	18.75	44	35.2	0.024
	Respiratory distress	72	77.4	21	65.6	93	74.4	0.187
X-ray	Normal	08	8.60	1	3.13	9	7.20	0.301
	Infiltrates	41	44.09	3	9.38	44	35.20	0.004
	Consolidation	41	44.09	23	71.88	64	51.20	0.007
	Effusion	3	3.22	5	15.63	08	6.40	0.026
TLC	Normal	28	30.11	09	28.00	37	29.60	0.832
TLC	Abnormal	65	69.89	23	72.00	88	70.40	0.832
Blood culture	Positive	13	13.97	03	09.37	16	12.8	0.501
Blood culture	Negative	80	86.02	29	90.62	109	87.20	0.501
Nasopharyngeal swab culture/(mPCR)	Positive	41	44.08	17	53.12	58	46.4	0.377
Nasopharyngeal swab culture/(mPCR)	Negative	52	55.91	15	46.87	67	53.6	0.377
Urine culture	Positive	04	4.30	0	00	04	3.2	0.572
Urine culture	Negative	89	95.70	32	100	121	96.8	0.572

(1) Community-acquired pneumonia (CAP) is a lower respiratory tract infection occurring in a child who has not resided in a hospital or health care facility in the preceding 14 days; (2) according to NFSH-3 children who received BCG, measles and three doses each of DPTand Polio (excluding Polio 0) are considered to be fully vaccinated; (3) 1--6 months: 6000--17,500 per mm blood, 7--24 months: 6000--17,000 per mm blood and 25--60 months: 5500--15,500 per mm blood; (4) <3 years by urinary catheterisation, >3 years from mid-stream. TLC: total leucocyte count.

A total of 16 (12.8%) patients had positive blood cultures with different organisms. Group A had higher blood culture positivity compared to Group B (13.9% vs. 9.3%). Nasopharyngeal bacterial growth (by NPS PCR gene detection plus culture) was found in 58 (46.4%) patients out of whom 41 (44.1%) were in Group A and 17 (53.1%) in Group B. Urine culture was found in only four (3.2%) patients all of whom belonged to Group A (Table 3). Various bacterial growths observed in blood and nasopharyngeal culture and RT-PCR of nasopharyngeal swab are shown in Table 4.

Table 4.

Growths in different cultures and PCR.

	Blood culture			p value	Nasopharyngeal culture /mPCR			p value	Urine culture
Growth	Group A N = 93	Group B N = 32	Total N = 125	p value	Group A N = 93	Group B N = 32	Total N = 125	p value	Group A N = 93	Group B N = 32	Total N = 125	p value
Staphylococcus aureus	01 (1.07%)	01 (3.15%)	02 (1.6%)	0.448	06 (6.45%)	03 (9.38%)	09 (7.2%)	0.581	–	–	–
Streptococcus pneumoniae	04 (4.3%)	02 (6.2%)	06 (4.8%)	0.645	10 (10.75%)	05 (15.6%)	15 (12%)	0.464	–	–	–
Escherichia coli	02 (2.1%)	0	02 (1.6%)	1.000	06 (6.45%)	02 (6.25%)	08 (6.4%)	0.968	03 (3.2%)	0	03 (2.4%)	0.569
Klebsiella pneumoniae	01 (1.07%)	0	01 (0.8%)	1.000	04 (4.30%)	01 (3.1%)	05 (4%)	1.000	01 (1.07%)	0	01 (0.8%)	1.000
Pseudomonas	01 (1.07%)	0	01 (0.8%)	1.000	03 (3.2%)	01 (3.1%)	04 (3.2%)	1.000
Haemophilus influenza	02 (2.1%)	0	02 (1.6%)	1.000	06 (6.45%)	01 (3.1%)	7 (5.6%)	0.480
CONS	01 (1.07%)	0	01 (0.8%)	1.000	04 (4.3%)	01 (3.1%)	05 (4.0%)	1.000
Citrobacter koseri	01 (1.07%)	0	01 (0.8%)	1.000	02 (2.15%)	01 (3.1%)	3 (2.4%)	1.000
Chlamydia pneumoniae	0	0	0	N/A	00	02 (6.2%)	02 (1.6%)	0.064
Total	13 (13.97%)	03 (9.37%)	016 (12.8%)		41 (44.08%)	17 (53.12%)	58 (46.4%)		04 (4.3%)	00	04 (3.25%)

mPCR: multiplex polymerase chain reaction.

Categorical variables were presented in number and percentage (%) and continuous variables were presented as mean ± SD and median. Qualitative variables were compared using the χ² test/Fisher's exact test as appropriate. A p value of < 0.05 was considered statistically significant. Data were entered in MS EXCEL spread sheet and analysed using Statistical Package for Social Sciences (SPSS) version 16.0 and Graphpad Instat.

Discussion

In recent years, the incidence of complicated and severe pneumonia seems to be increasing. Aetiological factors vary with age, source of infection (community vs. hospital acquired pneumonia) and underlying host defects (e.g. immunodeficiency). Viruses are the most common cause in preschool children, although in many cases more than one causative agent can be identified.²³

Our finding favours that radiological changes are more common in older children but we still cannot justify the use of chest radiography in making the diagnosis of pneumonia as the clinical diagnosis is more consistent than radiological diagnosis and the latter also has more chances of observer biasing. There is large variation in blood culture positivity rate in CAP around the world. Different studies have shown growth rates from 2.5% to 25%. These variations in various studies may be due to several factors such as immunity, nutrition, geographical region, timing and method of blood culture, aseptic precautions and vaccination status of patients amongst others.^24–27 Although nasopharyngeal PCR/culture has a higher yield than blood culture, in our view, this is only indicated in patients who are non-responsive to standard WHO treatment for CAP, especially in resource-limited environments.

A strength of the study is our simple, straight forward pin point approach towards the clinical spectrum of CAP in two different age groups. As our study was conducted in a rural region, its outcome is projectable to the whole population, as the majority live in rural areas. A limitation of our study is the uneven distribution of samples in groups, the inability to include babies <2 months of age, which is the most vulnerable age group for infective pneumonia, the lack of expert radiologists making some observational bias inevitable, and the inability to confirm a viral aetiology by PCR or other methods.

The study concluded that both age groups had almost the same signs and symptoms except the inability to feed or drink which is a common symptom of younger age group. Consolidation and effusion are more common in older age group while culture positivity is higher in younger age group. Risk factors for pneumonia in children include malnutrition, top feeding during first six months of life and having no immunisation.

Footnotes

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.

ORCID iD

Dinesh Kumar

References

Seaton

Leitch

Seaton

. Crofton and Douglas's respiratory diseases, 5th ed. New York, NY: John Wiley & Sons, 2008;

Black

Morris

Bryce

. Where and why are 10 million children dying every year?. Lancet 2003; 361: 2226–2234.

United Nations Inter Agency Group for Child Mortality Estimation. UNICEF, United Nations population division: levels and trends in child mortality reports 2014, https://www.unicef.org/media/files/Levels_and_Trends_in_Child_ Mortality_2014.pdf (accessed 25 December 2017).

World Health Organisation, Global Health Observatory. Proportions of child deaths by cause. World Health Organisation, Geneva, http://www.who.int/gho/child_health/prevention/pneumonia/en (2016, accessed 4 December 2017).

Davies

. Community-acquired pneumonia in children. Paediatr Child Health 2003; 8: 616–619.

Margolis

. Does this infant have pneumonia?. JAMA 1998; 279: 308–313.

Bachur

Perry

Harper

. Occult pneumonias: empiric chest radiographs in febrile children with leukocytosis. Ann Emerg Med 1999; 33: 166–173.

Bennett NJ. Clinical presentation. In: Steele RW (ed.) Paediatric Pneumonia update 2014, http://emedicine.medscape.com/article/967822-clinical (accessed 3 December 2017).

Ghai OP. Ghai essential paediatrics: diseases of respiratory system. 8th ed. New Delhi: CBS, 2013, p.377.

10.

Courtoy

Lande

Turner

. Accuracy of radiographic differentiation of bacterial from nonbacterial pneumonia. Clin Pediatr 1989; 28: 261–264.

11.

Bradley

Byington

Shah

, et al. 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.

12.

Esposito

Cohen

Domingo

, et al. Antibiotic therapy for pediatric community-acquired pneumonia. Pediatr Infect Dis J 2012; 31: e78–e85.

13.

Kennedy

Bates

Wright

, et al. Do emergency department blood cultures change practice in patients with pneumonia?. Ann Emerg Med 2005; 46: 105.

14.

Campbell

Marrie

Anstey

, et al. The contribution of blood cultures to the clinical management of adult patients admitted to the hospital with community-acquired pneumonia. Chest 2003; 123: 1142–1150.

15.

Corbo

Friedman

Bijur

, et al. Limited usefulness of initial blood cultures in community acquired pneumonia. Emerg Med J 2004; 21: 446–448.

16.

Revised WHO classification and treatment of childhood pneumonia at health facilities evidence summaries. In: Apps.who.int, https://apps.who.int/iris/bitstream/handle/10665/137319/9789241507813_eng.pdf (2020 accessed 1 July 2020).

17.

World Health Organization. The management of acute respiratory infections in children: practical guidelines for outpatient care, Geneva: WHO, (1995, accessed 25 December 2017). .

18.

NFHS-3 (2005–06) National Family Health Survey India. International Institute for Population Sciences (IIPS) and Macro International, Mumbai, India, 2007.

19.

Cherian

Mulholland

Carlin

, et al. Standardized interpretation of paediatric chest radiographs for the diagnosis of pneumonia in epidemiological studies. Bull World Health Organ 2005; 83: 353.

20.

Nathan DG and Oski FA. Hematology of infancy and childhood. 2nd ed. Philadelphia, PA: WB Saunders, 1981, pp.1552–1574.

21.

Guidelines for collection, storage and transportation of human clinical samples for laboratory diagnosis of influenza, National Centre for Disease Control, New Delhi, India.

22.

Strålin

Bäckman

Holmberg

, et al. Design of a multiplex PCR for Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae and Chlamydophilapneumoniae to be used on sputum samples. APMIS 2005; 113: 99–111.

23.

Harris

Clark

Coote

, et al. British Thoracic Society Standards of Care Committee. British Thoracic Society guidelines for the management of community acquired pneumonia in children: update 2011. Thorax 2011; 66(Suppl 2): 1–23. ii.

24.

Shekhawat

Sharma

Singh

, et al. Bacteriological and clinical profile of community acquired pneumonia in hospitalised children with associated co-morbidity in a tertiary care centre of Western Rajasthan, India. Int J Contemp Pediatr 2016; 3: 1380–1384.

25.

Mathew

Singhi

Ray

, et al. Etiology of community acquired pneumonia among children in India: prospective, cohort study. J Glob Health 2015, pp. 5: 1–9.

26.

Iroh Tam

Bernstein

, et al. Blood culture in evaluation of pediatric community-acquired pneumonia: a systematic review and meta-analysis. Hosp Pediatr 2015; 5: 324–336.

27.

Das

Patgiri

Lahari

, et al. Bacterial pathogens associated with community-acquired pneumonia in children aged below five years. Indian Pediatr 2016; 53: 225–227.