Introduction

Community-acquired pneumonia has been a serious health issue, particularly among the pediatric age group, and is considered to be one of the major causes responsible for hospital admissions ¹. It has been a significant cause of respiratory illness and has resulted in numerous pediatric deaths in developing countries. Prematurity, undernutrition, poor socioeconomic conditions, and exposure to tobacco smoke are the components that raise the rates and severity of pneumonia in pediatric populations ². Streptococcus pneumoniae, Staphylococcus aureus, Mycoplasma pneumoniae, and Hemophilus influenzae are among the most common organisms responsible for CAP ¹. Among them, M. pneumoniae   has been considered one of the deadliest ones responsible for hospital admissions. M. pneumoniae   is a widespread bacterial pathogen that has been associated with various clinical manifestations, including pneumonia, encephalitis, and extra-CNS manifestations like Stevens-Johnson syndrome ^3,4. Mycoplasma pneumoniae (MP) is frequently linked to epidemics in communities and healthcare settings, notably in school-age children and adolescents ⁵. But as diagnostic testing is typically based on serology or non-standardized molecular techniques, the prevalence and epidemiology of hospitalized community-acquired pneumonia (CAP) owing to Mycoplasma pneumoniae are poorly recognized ⁶. Clinically, children with Mycoplasma pneumoniae CAP exhibited generalized features of fever, cough, diarrhea, and other vague symptoms ⁷ that were insufficiently distinguishable to discriminate CAP caused by Mycoplasma pneumoniae from other etiologies. On multivariate analysis, the signs and symptoms linked to Mycoplasma pneumoniae CAP are comparable to those seen with other microorganisms, such as virus infections such as influenza. Additionally, clinical characteristics that are independently linked to MP detection, including rales, have historically been linked to common bacterial illnesses ⁸. According to several epidemiological studies, M. pneumoniae infection rates range from 1.3% to 50%, and during epidemics, infection rates may exceed 50% ⁹. In children under the age of five who have pneumonia, case-control statistics show that >1 microorganism was found in 93.0% of cases and 74.1% of controls ¹⁰. Therefore, identifying the etiological profile of M. pneumoniae pneumonia and the connection to clinical characteristics may help to improve the management and treatment. Mycoplasma pneumonia is generally a benign illness, although it can have several pulmonary and extrapulmonary complications, particularly in young children and the elderly, such as ARDS, lung abscess, necrotizing pneumonitis, respiratory failure, myocarditis, aseptic meningitis, hemolysis, septic arthritis, hepatitis, pancreatitis, conjunctivitis, glomerulonephritis, and so on ¹¹. The link between asthma and recurrent episodes of wheezing has been demonstrated in numerous studies. The initial study that specifically correlated viral illness and mycoplasmal infection to repeated bouts of wheezing in asthmatic children was published in 1970 by Berkovich et al. ¹². Of the 84 patients, 27 (32%) had corroboration of infection with either M. pneumoniae or a respiratory virus proven by serology. In a study by Lieberman et al., a large number of patients (18%) were discovered to suffer from M. pneumoniae pneumonia and were hospitalized for an acute exacerbation of bronchial asthma ¹³. In another trial by Biscardi et al., an actual M. pneumoniae infection was located in 20% ¹⁴ (24/119) of the subjects already diagnosed with asthma during their recent exacerbation. Acute MP infection was identified in 26 (50%) of the 51 cases who were having their first episode of asthma ¹⁴. It has been hypothesized that M. pneumoniae-related community-acquired pneumonia in infancy is linked to a higher frequency of asthma. In 1994, Yano et al. ¹⁵ documented a patient whose earlier acute mycoplasmal respiratory infection led to the beginning of bronchial asthma. M. pneumoniae may yet be isolated from respiratory secretions even after receiving excellent antibiotic therapy. When compared to controls, pulmonary structural abnormalities indicative of minor airway obstruction was seen much more frequently in the first 1-2 years following M. pneumoniae infection ¹⁶. Continued Mycoplasma pneumoniae affection causes lower expiratory flow rates and increased airway hyperresponsiveness in those without asthma ¹⁷.  Because of the ample prevalence and fatal complications of community acquired pneumonia, there is a need to identify cases of Mycoplasma pneuemonia and treat them optimally to minimize the long-term consequences.

Material and Method

This was a retrospective cohort study conducted from October 2019 to October 2021 at the Pediatric Outpatient and In-Patient Department and Pediatric Infectious Diseases Clinic, Jawaharlal Nehru Medical College and Hospital, Aligarh Muslim University, Aligarh, Uttar Pradesh, India, on the prevalence of mycoplasma-related community-acquired pneumonia in 38 patients enrolled for the trial based on inclusion and exclusion criteria. 2 patients out of 38 expired during the hospital stay, and 4 patients were lost to follow-up. Therefore, a total of 32 patients were evaluated for analysis. The details of the study have been described as follows: 

Inclusion Criteria

Any case of Community-Acquired Pneumonia aged 1 to 14 years.

Exclusion Criteria

Patients with co-morbidities such as heart disease (Congenital or Acquired), Diabetes, and known respiratory illnesses like Chronic Lung disease, Asthma, Cystic Fibrosis, Tuberculosis, Developmental Delay, Obesity, and Syndromic children like Downs Syndrome.

Consent for the study

Informed parental consent was signed by the parents of the patients willing to participate in the trial.

Methodology

The study included all community-acquired pneumonia (CAP) cases that were presented to the inpatient and outpatient clinics of the Department of Pediatrics between October 2019 and October 2020, fulfilling the inclusion criteria. The diagnosis of community-acquired pneumonia was made as per the WHO criteria.

On the first day of the visit or admission, 2 ml of venous blood was drawn into a red-top vial while following all aseptic procedures, and it was quickly transported to the J.N. Medical College Immunology Lab in the Department of Microbiology. Following centrifugation of the samples, the serum was extracted with a pipette and kept at -20°C in a deep freezer for up to six months.

All the patients received treatment following standard guidelines.

Statistical Methods

SPSS software was used to capture and analyze all data. The chi-square test was employed to assess categorical data that was presented as numbers and percentages. The mean and standard deviation were used to express continuous variables with a normal distribution. The differences were calculated using the t-test. A statistically significant difference was defined as a difference of P 0.05. 

Observation and Result

Table 1: Demographic parameters of patients with CAP.

 Demographic parameter are depicted in table 1. Table 2 depicts that out of a total of 32 patients (n=32), 22 patients (68.75%) had fever and cough, 17 (53.13%) patients had wheeze, 8 (25%) patients had rhinorrhoea and cyanosis, 19 (59.38%) patients had chest retractions, 32 (100%) patients had tachypnoea. The mean and SD of the temperature and SpO2 were 99.89 ± 0.92 and 92.94 ± 5.01 respectively. 

Figure 1: Age Distribution. Click here to view figure

Figure 2: Sex Distribution Click here to view figure

Table 2: Clinical signs and symptoms among CAP

Figure 3: Signs and Symptoms Click here to view figure

Table 3: Radiological findings among CAP

It is clear from table 3 that out of a total of 32 patients, 10 patients (31.25%) had diffused reticular pattern, 19 (20.65%) patients had lobar consolidation, 3 (9.38%) patients had para-hilar infiltration and 0 patients had hyperinflated lung fields.            

Figure 4: Radiological Findings Click here to view figure

Table 4: Sub-group analysis among CAP (between IgM + and IgM -)

It is clear from table 4 that the mean and SD of age in the M. pneumoniae   Ig M +ve and Ig M – ve group is 2.84 ± 2.13 and 4.00 ± 3.94 respectively with P = 0.529. Out of the total of 32 patients, 5 patients (15.625%) were M. pneumoniae   Ig M +ve and 27 patients (84.375%) were M. pneumoniae   Ig M –ve. Out of the total of 5 Ig M +ve patients, 4 patients (80%) were in the age group 1-5 yrs and 1 patient (20%) was between 5-10 yrs of age whereas no patient was in the age group 10-14 yrs. Furthermore, out of a total of 27 Ig M –ve patients, 20 patients (74.07%) were in the age group 1-5 yrs, 4 patients (14.81%) were in the age group 5-10 yrs and 3 patients (11.11%) were between 10-14 yrs of age. Based on sex, 2 patients (40%) were M. pneumoniae Ig M +ve among males whereas 15 male patients (55.56%) were M. pneumoniae   Ig M –ve. Out of a total of 17 female patients, 3 (60%) were M. pneumoniae   Ig M +ve and 12 (44.44%) were M. pneumoniae   Ig M –ve with P = 0.522. The mean and SD of weight among the M. pneumoniae   Ig M + ve group is 12.06 ± 5.35 whereas it was 14.15 ± 7.84 In the Ig M –ve group with P = 0.574. The mean and SD of the height of the patients among Ig M + ve and –ve groups were 84.80 ± 17.82 and 91.59 ± 23.93 respectively with P = 0.552. The mean and SD of BMI among M. pneumoniae Ig M + ve and – ve were 16.07 ± 1.97 and 15.86 ± 2.18 respectively with P = 0.843. Out of the total patients with family H/o wheeze, 3 patients (60%) were M. pneumoniae   Ig M + ve and 8 ( 29.62%) patients were M. pneumoniae   Ig M –ve with P = 0.189. Among the total hospitalized patients, 2 (40%) patients were M. pneumoniae   Ig M + ve and 18 (66%) were M. pneumoniae   Ig M –ve with P = 0.257. 

Figure 5: Age distribution among CAP Click here to view figure

Figure 6: Demographic distribution on the basis of sex on Ig M status Click here to view figure

Table 5: Signs and symptoms among IgM+ and IgM- subgroups (CAP)

It is clear from Table 5 that out of the total of 5 (100%) M. pneumoniae   Ig M +ve patients, 5 (100%) patients had fever, cough, and tachypnea; 4 (80%) patients had wheeze; 3 patients (60%) had rhinorrhoea; 2 (40%) had chest retractions; no patient had cyanosis. The mean and standard deviation of temperature was 100.18 0.64, and the mean and standard deviation of Spo2 was 95.40 2.07. There were 17 (62.96%) patients with fever, cough, and chest retractions; 13 (48.15%) with wheezing; 5 (18.52%) with rhinorrhoea; 27 (100%) with tachypnea; and 8 (29.63%) with cyanosis. The mean and SD of temperature and Spo2 in the M. pneumoniae  -Ig M-ve group were 99.83  0.96 and 92.48   5.28, respectively. The corresponding P values of fever, cough, wheeze, rhinorrhoea, chest retractions, tachypnoea, cyanosis, mean temperature, and Spo2 in both M. pneumoniae   Ig M +ve and -ve groups were 0.100, 0.100, 0.189, 0.049, 0.336, NA, 0.159, 0.449, and 0.237, respectively.

Figure 7: Signs and Symptoms among CAP Click here to view figure

Table 6: Radiological findings among IgM+ and IgM- subgroups (CAP)

It is clear from Table 6 that out of a total of 5 M. pneumoniae   Ig M +ve patients, no patient had a hyperinflated lung field, whereas 2 (40%) patients had a diffuse reticular pattern and lobar consolidation, and 1 (20%) patient had para hilar infiltration. In the M. pneumoniae   Ig M-ve group, no patient had a hyperinflated lung field; 8 (29.63%) patients had a diffuse reticular pattern; 17 (62.96%) patients had lobar consolidation, and 2 (7.41%) patients had para hilar infiltration. In both the M. pneumoniae Ig M + ve and – ve groups, the corresponding P values were NA, 0.645, 0.336, and 0.374, respectively.

Figure 8: Radiological findings among CAP Click here to view figure

Discussion

Based on age, the majority of patients, i.e., 24 (75%) patients with CAP, were 1–5 years of age. This finding corresponds to previous studies that demonstrate that CAP is more prevalent in young children. With a frequency of 34 to 40 cases per 1,000 children in Europe and North America, CAP has been among the most prevalent severe illnesses in children ^18,19,20.

Although CAP-related deaths are uncommon in developed nations, lower respiratory tract infection is a prominent cause of childhood deaths in developing nations ^21,22. However, out of the total 32 cases, only 5 (15%) patients were M. pneumoniae   Ig M positive, and the rest 27 (85%) cases were M. pneumoniae   Ig M negative. The majority of the 5 (15%) M. pneumoniae -IgM+ patients were between the ages of 1 and 5 years old. However, this does not hold true with data from previous studies, which demonstrated that most of the M. pneumoniae   cases prevail in children older than 5 years ²³. Therefore, it has been advised to conduct further studies on a large sample size in this domain to find out the likely age group affected by M. pneumoniae   and the possible reason behind its occurrence in this particular age group.

Based on sex, 17 (53.13%) patients were males suffering from CAP and 15 (46.88%) patients were females. This finding is in agreement with previous studies which support the notion that males are more likely to suffer from lower RTIs. The reviewed data also showed that males tend to have a more severe course of respiratory tract infection than females, resulting in increased deaths in males, particularly in community-acquired pneumonia cases. The involvement of sex hormones in immune system regulation may be responsible for observed sex variations in the occurrence and intensity of certain forms of RTIs, particularly in adolescents and adults ²⁴. However, out of a total of 5 (15%) M. pneumoniae   IgM +ve patients, 3 were female and 2 were male which may be an incidental finding and does not have any clinical significance. 8 (25%) out of a total of 32 patients had family H/o wheeze of which 3 children were M. pneumoniae   Ig M +ve. In another trial by Biscardi et, acute M pneumoniae infection was located in 20% ¹⁴ (24/119) of the subjects already diagnosed with asthma during their recent exacerbation. Acute M. pneumoniae was identified in 26 (50%) of the 51 patients who were having their first episode of asthma[14]. However, given hospitalization, 20 (62%) patients required hospitalization indicating the severe nature of CAP infection.  Bhat et al ²⁵ in their study put forth that most of the CAP cases requiring hospitalization belong to the under-5 age group. In our study, most of the children hospitalized had etiologies other than M. pneumoniae, and only 2 patients of the total 5 M. pneumoniae Ig M +ve required hospitalization.

Based on clinical features, all 32 patients had fast breathing (100%); 22 (68.75%) patients had fever and cough; 19 (59.38%) had chest retractions; 17 (53.13%) had wheeze, and 8 (25%) patients had rhinorrhoea and cyanosis. The mean temperature and SpO2 were 99.89  0.92 and 92.94  5.01, respectively. Five of the 22 (68.75%) patients with fever and cough were M. pneumoniae   Ig M +ve, while the remaining 17 (62.96%) were M. pneumoniae   Ig M -ve. There were 5 M. pneumoniae IgM+ve and 27 M. pneumoniae   Ig M -ve patients among the 32 patients with tachypnea. There were two M. pneumoniae positive patients and seventeen M. pneumoniae   Ig M negative patients among the 19 patients who had chest retractions. Four of the 17 wheezing patients tested positive for M. pneumoniae IgM+ve while 13 tested negatives. Three of the rhinorrhea patients had M. pneumoniae IgM+ve and five had M. pneumoniae IgM -ve. None of the eight cyanotic patients tested positive for IgM. To help medical and non-medical healthcare professionals diagnose lower respiratory tract infections (LRTIs) in the absence of radiological evidence, the WHO has created an algorithm ²⁶ This algorithm is still helpful as a clinical tool in the UK, even though it was created for use in developing nations. Tachypnoea is highlighted as a key sign of pneumonia in the WHO algorithm, which is consistent with our study as well. Tachypnoea, as defined by the WHO, has a sensitivity of 74% with 67% specificity for radiologically diagnosed pneumonia. When dealing with children who menstruate early, doctors must be cautious. In children with co-morbid illnesses like asthma, tachypnea as a marker of pneumonia must be used with caution because it can indicate a worsening of the underlying condition. Even when it is present together with a fever and a cough, an antibiotic may not always be necessary ²⁷. It has also been discovered that a high temperature in young children (up to 3 years old) can indicate pneumonia ^28,29. A sign of bacterial pneumonia is a temperature greater than 38.5 °C ³⁰. According to the BTS recommendations, pneumonia is indicated in children under the age of three when a fever >38.5 °C, chest retractions, and respiratory rate >50 are present. In older children, breathing difficulties by themselves are a more reliable indicator. However, the clinical presentation of M. pneumonia is often compared with other atypical microorganisms, particularly Chlamydia pneumoniae, viruses, and bacteria. M. pneumoniae may ³¹ also be found in the lungs concurrently with other microbes, and there is some corroboration from human and animal studies showing that infection with M. pneumoniae may either initiate or possibly flare up the subsequent infections with different respiratory pathogens ³², such as S. pyogenes and Neisseria meningitides. Immunosuppression or a change in respiratory tract commensals caused by the co-existence of M. pneumoniae are two possible explanations for such an agonistic effect. The acute febrile phase typically lasts a week in uncomplicated cases, whereas the cough and malaise may exceed two weeks. If antibiotics are taken early in the disease, the duration of symptoms and signs will typically be shorter. The clinical features observed in our study did not vary greatly from those mentioned in other studies ^33,34,35 except for tachypnea being the most common symptom, whereas it was fever and cough in others.

M pneumoniae pneumonia is a significant contributor to acute respiratory tract infections, particularly when considered as a possible cause of the clinical condition known as atypical pneumonia. Early diagnosis of M. pneumoniae infection is crucial to enhancing the identification of people in need of treatment and avoiding needless antibiotic administration. The most popular technique for identifying M. pneumoniae infections is serology. Furthermore, as antibody reactions can frequently be found even when the organism may not be collected through cultures, antibody identification is a more sensitive marker of Mp infection than the organism itself ⁵⁴. However, the sensitivity and specificity of ELISA Ig M for M. pneumoniae infection were 84.62% and 81.33% respectively ⁵⁵. M. pneumoniae-specific IgM antibodies may not be detectable for the initial one week of the illness but remain in the blood for several months after infection ⁵⁷. As a result, a single test of serology in an acute phase of the illness is not necessarily a reliable diagnostic method for acute M. pneumoniae infection. The earlier study found that the first positive test rate for M. pneumoniae IgM upon hospital admission was 63.6%, with the cumulative positive test rate increasing to 97.5% one week later ⁵⁷. Two serologies with the conversion from initial negative to positive or a rise in antibody titers (i.e. a two times increase in M. pneumoniae IgM or a four times increase in M. pneumoniae IgG) between the acute and convalescent phase point towards a very reliable diagnosis ⁵⁸. However, in individuals with compromised immunity, such as young children, the immunological response may be too weak to generate the antibodies ⁵⁸ as seen in our study where most of the patients were between 1-5 yrs of age. Therefore, serology alone should not be considered as a basis for diagnosing M. pneumonia and specific antibiotics must be considered even in serology-negative cases when suspicion of atypical pneumonia particularly M. pneumonia is high.

Although there were certain limitations to our study on the grounds of infrastructure, resources, financial support, and small sample size, this study may serve as a relay and open a new door for further research on a large sample size with better tools, research techniques, and more appropriate parameters to obtain a more precise and authentic result.

Conclusion

 Mycoplasma pneumoniae CAP exhibited generalized features of fever, cough, diarrhea, and other vague symptoms with radiological findings of Hyperinflated lung field, Diffuse reticular pattern, Lobar consolidation, and Para hilar infiltration.

It has been concluded from the above study that the prevalence of Mycoplasma pneumoniae in community-acquired pneumonia cases based on serology is low. However, since serology is not 100% sensitive and specific and may vary in titers serology alone. Owing to the severity of the disease, a differential diagnosis of M. pneumoniae pneumonia must always be kept in consideration particularly in unremitting cases of CAP by common antibiotics where suspicion of M. pneumonia is high.

Acknowledgement

I cannot express enough thanks to my committee for their continued support and encouragement. 

Conflict of interest

The authors have no conflict of interest.

Funding support

The authors received no external funding support for this research work.

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