The global lockdowns and implementation of non-pharmaceutical interventions (NPIs) against COVID-19 during the pandemic led to the decreased circulation of several respiratory pathogens, including influenza and Mycoplasma pneumoniae (M. pneumoniae).1 Cases of M. pneumoniae, known for epidemic-level outbreaks every 1-3 years, suddenly stopped occurring, with surveillance reports showing a dramatic drop in prevalence since March 2020.1,2 While influenza and other causes of respiratory infections resurged in the years following the relaxing of NPIs, surveillance numbers for M. pneumoniae remained low until recently.1 Should M. pneumoniae revert to pre-pandemic levels, vigilant surveillance and testing is going to be important in determining the understanding of the spread of this illness and the appropriate treatment intervention.
Uptick in Respiratory Tract Infections (RTIs) Post Pandemic
A recent surge of hospitalizations due to a respiratory illness mostly impacting children in China has raised concerns of international organizations including the World Health Organization (WHO), reminiscent of late 2019.3 Unlike the novel coronavirus, this illness and the increase in cases of childhood pneumonia reported seem to be attributable to a mix of RTIs that tend to peak in the cold months. These include SARS-CoV-2 virus, influenza virus, and respiratory syncytial virus (RSV), but also, and more specifically underlying the recent uptick in pneumonia cases, the bacterial pathogen – M. pneumoniae.3

As of late November 2023, surveillance data monitoring the incidence of M. pneumoniae cases from 45 sites in 24 countries in Europe, Asia, the Americas, and Oceania showed there was an average increase of more than fourfold, with larger increases in Asia and Europe.4 Now, the number of new M. pneumoniae infections has reached an epidemic level in Denmark.5 Due to this increase, the Centers for Disease Control and Prevention (CDC) is looking into recent reports of M. pneumoniae infections among children in the United States.6
Currently in countries where M. pneumoniae has re-emerged, case numbers are comparable to endemic numbers, but must continue to be monitored to assess whether cases may result in an exceptionally large wave of infections. This is especially important following the measures taken to slow the spread of COVID-19, as due to reduced exposure and loss of herd immunity, it will be difficult to predict whether the re-emergence of infections may lead to an increase in typically rare cases of severe disease.4
M. Pneumoniae Clinical Presentation
Infections caused by M. pneumoniae can affect the upper or lower respiratory tract and can manifest in several ways including tracheobronchitis, pharyngitis, and pneumonia. Onset can be gradual, slowly progressing to a higher fever and a persistent cough, and it can last for several weeks. Symptoms in children under the age of five can include sneezing, stuffy or runny nose, sore throat, watery eyes, wheezing, vomiting, and diarrhea, while in those over this age fever and chills, coughing, feeling tired, and shortness of breath are more common. While M. pneumoniae infections tend to be mild, they can lead to severe complications and hospitalizations.7 Young children are more likely to have cases that progress to pneumonia, especially if they’ve never been exposed to the bacterium before or have weak immune systems.4
| Symptoms of M. Pneumoniae | |
| Children under the age 5 | People over the age 5 |
| Sneezing or wheezing | Fever |
| Stuffy or runny nose | Chills |
| Sore throat | Coughing |
| Watery eyes | Fatigue |
| Vomiting or diarrhea | Shortness of breath |
Pneumonia cases resulting from M. pneumoniae infection are often termed “atypical,” due to different clinical presentation and requirement for different treatment compared to what are considered “typical” cases of pneumonia. As these bacteria do not have a rigid cell wall, the antibiotics such as penicillin that target the cell wall cannot be used for treatment.11 Therefore, accurate diagnosis of infections is crucial for treatment selection.
M. pneumoniae infection outbreaks occur mostly in crowded settings like schools, college residence halls, military training facilities, long-term care facilities, and hospitals.7 With no formal national reporting or surveillance systems, the exact incidence numbers are likely higher than those estimated at 2 million in the United States and those reported in other countries.8
Polymerase Chain Reaction (PCR) Testing in RTIs
PCR-based molecular diagnostic tests are considered the gold standard for the detection of pathogens due to the high sensitivity and specificity and fast turnaround time they offer relative to other testing modalities. Most respiratory bacterial pathogens are often routinely detected using culture. However, pathogens such as M. pneumoniae or Chlamydia pneumoniae require special culturing conditions, are time consuming, and may require weeks to obtain an isolate.12,13 Due to the specific nature of these pathogens, using culture for diagnostics has high false negativity rate and does not provide optimal time to result for treatment decisions. For these reasons, PCR-based molecular testing is the preferred method for diagnostic testing of acute infections for these pathogens.12,13

Many respiratory infections have similar clinical presentations, making diagnostic testing an important step in quickly distinguishing the underlying cause and helping determine appropriate treatment options.9 Real-time PCR-based syndromic panels for RTIs have the advantage of simultaneously detecting and differentiating critical respiratory pathogens including M. pneumoniae and other bacteria, viruses, and even fungi within hours, with higher sensitivity and specificity, and significantly shorter time to results compared to methods relying on culture or microscopy. The availability of fast, highly accurate results following a single sample collection enables for informed decisions about therapeutic interventions that may help decrease antibiotic therapy duration, reduce the number of additional, often invasive tests, and shorten hospital stays.10
Thermo Fisher Scientific offers several in vitro diagnostic PCR-based molecular testing solutions for respiratory pathogens. These can help maximize your efficiency and minimize operational costs, with multiple targets from a single sample. Early and accurate detection and differentiation is crucial in understanding the cause of infection, lending confidence in results, and determining the next steps.
Separately, Thermo Fisher also offers research use only solutions, mainly used for respiratory pathogen surveillance or research. These enable labs to research multiple pathogens, and are available in a wide range of formats to accommodate scalability and customization.
As cases of respiratory infections and pneumonia continue to rise worldwide, use of real-time PCR for molecular diagnostics has the potential to improve patient care by rapidly determining the disease-causing pathogen, reducing prescribing of unnecessary antibiotics, and earlier, appropriate selection of therapeutic treatment options.
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References:
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- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9101966/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976882/
- https://www.who.int/europe/news/item/15-12-2023-respiratory-infectious-diseases-on-the-rise-across-who-european-region
- https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(23)00344-0/fulltext
- https://www.ssi.dk/aktuelt/nyheder/2023/der-er-epidemi-med-mycoplasmainfektioner-ogsaa-kendt-som-kold-lungebetaendelse
- https://www.cdc.gov/pneumonia/atypical/mycoplasma/surv-reporting.html#:~:text=CDC%20is%20looking%20into%20recent,think%20their%20child%20has%20pneumonia.
- https://www.cdc.gov/pneumonia/atypical/mycoplasma/about/index.html
- https://www.cdc.gov/pneumonia/atypical/mycoplasma/surv-reporting.html
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120591/
- https://pubmed.ncbi.nlm.nih.gov/25152311/
- https://www.cdc.gov/pneumonia/atypical/mycoplasma/hcp/disease-specifics.html
- https://www.cdc.gov/pneumonia/atypical/mycoplasma/hcp/diagnostic-methods.html
- https://www.cdc.gov/pneumonia/atypical/cpneumoniae/hcp/diagnostic.html