Silent emergence of Mycoplasma pneumonia from 2022 to 2024

INTRODUCTION

Mycoplasma pneumoniae is an atypical bacterium that causes infections, including acute respiratory infections, pharyngitis, tracheobronchitis, wheezing, and pneumonia. Among these, tracheobronchitis (a chest cold) is the most common, while pneumonia (a lung infection) is less common,^[1] especially in children aged 5–15 years.^[2] During the pandemic, the number of cases detected worldwide decreased significantly. Whereas the revival of virtually all respiratory-related diseases began slowly in 2021, the prevalence of M. pneumoniae stayed very low through June 2023, when a significant upsurge of cases was documented worldwide.^[3]

In Taiwan, during the COVID-19 pandemic, all other notifiable diseases (Influenza, invasive pneumococcal disease [IPD], pertussis, and enterovirus) were significantly decreased. The emergence of M. pneumoniae, a call of immune debt among individuals, results resurgence of several infectious diseases, leading to large epidemics in post-pandemic areas. The pandemic has led to a shift in both the disease burden and seasonality of infectious diseases. Respiratory syncytial virus (RSV) is most prevalent during the rainy season in subtropical and tropical regions, and its peak incidence occurs during winter in temperate regions. Out-of-season RSV resurgences were reported in both the southern and northern hemispheres following a mild winter during the COVID-19 pandemic.^[4] Metagenomic analysis of M. pneumoniae shows EC1 in P1-1 and EC2 (Enzyme Comission number) in P1-2; since 2010, EC1 has been isolated throughout Asian countries; in contrast, EC2 emerged first in 2019 in Taiwan. EC2 shows resistance to macrolides due to a mutation in A2063G of the 23S ribosomal RNA.^[5] Countries such as Denmark, the Netherlands, France, and Spain also faced a rapid increase in M. pneumoniae at the end of 2023.^[6-9]

Central nervous system (CNS) abnormalities and consequences are most typically observed and documented in M. pneumoniae episodes. Patients with M. pneumoniae illness may experience varied degrees of neurological problems at a rate of roughly 6–7%.^[3] Neurological symptoms include encephalitis, acute disseminated encephalomyelitis, transverse myelitis, Guillain–Barré syndrome, and thromboembolic stroke. The duration between the onset of pulmonary and neurological symptoms ranges from 2 to 14 days. More than 80% of individuals with CNS abnormalities have a concurrent respiratory infection.^[10-12]

The introduction of non-pharmaceutical interventions against COVID-19 led to a rapid decline in outbreaks and a significant decrease in M pneumoniae incidence globally. In contrast to the pre-pandemic prevalence of M pneumoniae.^[2] implementing non-pharmaceutical.The data suggest that maintaining NPIs, such as hand hygiene and respiratory etiquette, after COVID-19 helped prevent M. pneumoniae transmission.^[13,14]

Macrolide resistance in M. pneumoniae, which has just one ribosomal operon, is determined by an antibiotic-targeting ribosomal mutation.^[15] There is no literature available on the natural resistance of tetracycline in M. pneumoniae; minocycline and doxycycline have shown better performance against macrolide-resistant M. pneumoniae.^[16]

MATERIALS AND METHODS

A retrospective study was conducted using polymerase chain reaction (PCR) analysis between January 2022 and December 2024 at Mani Microbiological Laboratory Pvt. Ltd., Bangalore, India, to investigate the delayed re-emergence of M. pneumoniae in the post-COVID-19 period. Over 19242 cases requested for respiratory tract infection test, it includes Influenza A, H1N1, Influenza B, Rhinovirus, Coronavirus NL63, Coronavirus 229E, Coronavirus oc43, Coronavirus HKU1, Parainfluenza 1-4, Bocavirus, Human Metapneumovirus A/B, M. pneumoniae, RSV A/B, Adenovirus, Enterovirus, Parechovirus, Cytomegalovirus, Streptococcus pneumoniae, Chlamydia pneumoniae, Staphylococcus aureus, Haemophilus influenzae type B, Pan-Fungal DNA with respiratory samples of throat and nasopharyngeal swab, sputum, endotracheal secretion (ET) and bronchoalveolar lavages (BAL). For multiplex, fast-track diagnosis of respiratory pathogens using the TaqMan probe assay, all specimens were collected according to routine standards from hospitals and laboratories.

Collected specimens were pre-treated, as per the samples type before extraction; includes n = 14,795 (throat and NP swab), n = 1219 (throat swab), n = 2047 (nasal swab), n = 245 (sputum), n = 135 (ET secretion), n = 485 (BAL fluid), n = 26 (BAL aspirate), n = 163 (pleural fluid, n = 4 (CSF), n = 71 (ET aspirate), n = 23 (BAL wash), n = 11 (lung biopsy), n = 8 (Pus), n = 6 (gastric fluid), n = 2 (lung abscess), n = 1 (splenic granuloma aspiration), and n = 1 (pericardial fluid).

RESULTS

Over 19,242 enrolments, M. pneumoniae DNA was detected in 790 (4.1%) individuals with severe community-acquired pneumonia (CAP) illness. In 2022, 6/3990 (0.15%) individuals were infected with M. pneumoniae; followed by 2023, 85/8240 (1.03%) had an infection. In the present year, 2024, the positivity rate has increased to 699/7012 (9.96%), higher than the previous year [Table 1]. In terms of patient gender, males (436/790, 55.18%) holds to be the increased M. pneumoniae cases; females (354/790, 44.8%) cases; a shrink ratio of (M/F) were (11:9) [Figure 1]. However, the infection of M. pneumoniae in the children aged 6–10 seems an elevated positive were noted; followed by 1–5 years age group had second most critically infected; 0^th day 3576 infants tested and turn out with 49 positives; 11–5 years had 100 (12.7%) infected children. Seventeen positive cases were observed among individuals aged 16–20 years. The overall percentage of positivity observed between the years 2022 and 2024 along with M. pneumonia are as follows: >10% of positivity was observed in RSV A/B, Rhinovirus and Adenovirus; >5% of positivity in Influenza A, B, Parainfluenza 1-4, HMPV and Streptococcus pneumonia; 1-5% positivity in Enterovirus, H1N1, Bocavirus, Parechovirus, Staphylococcus aureus, CMV and panfungal; <1% positivity in Coronovirus 229E, OC43, NL63 and Haemophilus influenza type B [Table 2].

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Figure 1:

Gender-wise distribution of Mycoplasma pneumoniae.

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Monthly distribution of pneumonia infection by M. pneumoniae

The positivity rate of M. pneumoniae in 2022–2023 increased 14-fold; in 2023–2024 nearly 8.2-fold; it has been gradually increasing in-between the years 2022 and 2024 (0.15–9.96% positives). In 2024 the data were as follows: January (12/583), February (20/513), March (10/486), April (15/267), May (10/176), June (7/211), July (23/427), August (41/816), September (84/1133), October (120/761), November (156/800), and December (201/838). The detection of M. pneumoniae among children increased consistently from July 2024 to December 2024. Among the tested, 24% of individuals were infected (December–2024) [Figure 2].

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Figure 2:

Month-wise distribution of Mycoplasma pneumoniae.

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M. pneumoniae in different age groups in the population

In 2022, there were six positives among 0th-day infants, with two cases; 1–5-year-olds had two cases, and 6–10-year-olds had one case. In 2023, 85 positives including 0^th day 10 infants detected positives; 1–5 years (20 cases), 6–10 years (32 cases), 11–15 years (6 cases), 21–25 years (one case), 31–35 years (two cases), 36–40 years (one case), 41–45 years (one case), 46–50 years (one case), 51–55 years (one case), 56–60 years (four cases), 66–70 years (two cases), 71–75 years (one case), 76–80 years (two cases), and 91-years-old (one case). In 2024, 0^th day 37 infants with M. pneumoniae; 1–5 years (197 cases), 6–10 years (275 cases), 11–15 years (93 cases), 16–20 years (17 cases), 21–25 years (six cases), 26–30 years (seven cases), 31–35 years (16 cases), 36–40 years(13 cases), 41–45 years (five cases), 46–50 years (five cases), 51–55 years (five cases), 56– 60 years (seven cases), 61–65 years (ten cases), 66–70 years (one case), 76–80 years (four cases), and 86–90 years (one case). The retrospective data analyzed from pre-COVID-19 and during the COVID-19 pandemic period, from 2018 to 2021, include 62/1156 M. pneumoniae-infected individuals [Figure 3].

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Figure 3:

Age-wise distribution of Mycoplasma pneumoniae.

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DISCUSSION

CAP has been correlated with elevated morbidity & mortality, and it poses significant risks to public health worldwide. Coughing and sneezing can distribute aerosols containing M. pneumoniae. It yields infections in both the upper and lower respiratory tracts, and the clinical signs are typically nonspecific. Tracheobronchitis is the most prevalent lower respiratory infection, followed by pharyngitis. Infections of the upper respiratory tract caused by M. pneumoniae. M. pneumoniae infections are typically self-limiting and mild, but they can progress to become serious or even life-threatening in some individuals M. pneumoniae has been causally associated with 40% of community-acquired pneumonia events in children below the age of five, where lower respiratory tract infections are a significant cause of morbidity and mortality.^[17,18]

Shin et al. observed the characteristics of M. pneumoniae in Korea (2020) with over 16.50% of infected cases and 69.67% of isolates were macrolide resistant in the epidemic period from 2019 to 2022; 0.86% of M. pneumoniae-positive instances had concurrent infections with non-normal floral pathogenic strains, including 158 Chlamydia pneumoniae, 23 Bordetella pertussis/parapertussis, and 2 Legionella pneumophila.^[19] Meyer et al. (2021) reported a differentiation of M. pneumoniae positive rates before the implementation of NPIs in India at 19/205 and after implementation at 16/153.^[20] According to Chaudhry et al., a study conducted in New Delhi found that 3.9% of 429 individuals tested positive for M. pneumoniae culture, with a 25.6% positive rate for immunoglobulin G and immunoglobulin M (IgM).^[21] According to Farooqui et al., the top five states contributing to India’s pneumonia burden were Uttar Pradesh (27,785/1,33,167), Bihar (23,202/91,578), Madhya Pradesh (13,043/52,250), Rajasthan (11,889/43,911), and Jharkhand (6,296/28,969).^[22 ] In 2024, over 88.5% of infected individuals were under the age of 5 years; 11.5% were 5–12 years old; 41.02% had wheezing; 53.8% had coryza; 5.12% had chest pain; there was no CNS/cardiovascular infection in the tested individuals.^[23] The enzyme-linked immunosorbent assay IgM for M. pneumoniae was positive in 33 (22%) instances, although only 15 (10%) patients showed positive amplification in PCR. Culturing was also undertaken on all of the samples; however, none of them were observed to be positive.^[24]

CONCLUSION

In conclusion, we found a higher prevalence of M. pneumoniae infection in children under the age of five years compared to adults. This data features the current status of the Mycoplasma pneumonia burden in the southern parts of India. Increasing access to RT-PCR-based molecular detection of the pathogen could facilitate a definitive diagnosis. The timely identification of M. pneumonia infection could reduce complications, including extrapulmonary manifestations, and could guide clinicians in the use of targeted therapy.