Mycoplasma outbreak in China? Maybe it's just an illusion

The incidence of false negative and false positive results for mycoplasma infection is high.

Written by Li Changqing (Doctor of Medicine, practicing physician in the United States)

Since the beginning of autumn, there have been continuous reports of major outbreaks of mycoplasma infections in China. More and more medical institutions and medical popularizers have joined the discussion, and mycoplasma infection has thus become a hot topic that has attracted much attention.

But I want to pour some cold water on this hot topic: Are the large number of patients currently diagnosed with mycoplasma infection really infected with mycoplasma?

The reason for this question is first of all based on the author's understanding of the overdiagnosis and treatment of mycoplasma infection in China. In previous years, many medical institutions, especially pediatrics, have used mycoplasma antibody testing as a routine item for respiratory diseases. Once positive, macrolide antibiotics are given for treatment, and the most commonly used one is azithromycin.

However, many medical guidelines, including some medical popularizers, have repeatedly mentioned that serological tests have poor diagnostic accuracy for mycoplasma infection, and their defects include false negatives in the early stages of the disease and false positives in the recovery period. According to a local survey by Panyu Maternal and Child Health Hospital, the probability of false negatives and false positives in serum antibody tests for mycoplasma infection is as high as more than 40%.

For this reason, authoritative organizations such as the Centers for Disease Control and Prevention (CDC) in the United States generally use nasal swab nucleic acid testing to diagnose mycoplasma infection. However, in China, this test is not a routine item in many medical institutions.

Another basis for this question comes from common sense about infectious diseases: in the autumn and winter seasons, although mycoplasma is a pathogen that cannot be ignored, it is not the most common one. According to statistics, the most common infection is still virus. In addition to the new coronavirus that everyone is already very familiar with, there are also rhinovirus, influenza virus, respiratory syncytial virus, adenovirus, seasonal coronavirus, etc. Especially for epidemic respiratory infections involving many regions across the country, virus epidemics are far more common than mycoplasma epidemics.

The reason why mycoplasma generally does not cause a pandemic is related to its biological characteristics. Compared with viruses and some common bacteria that infect the respiratory tract, mycoplasma replicates much slower. Ordinary bacteria only need 10 to 20 minutes to propagate, while mycoplasma takes six hours. Relatively speaking, the incubation period of mycoplasma is also longer, up to one to three weeks. Based on these characteristics, although mycoplasma infection can be transmitted through droplets and contact, the transmission speed is much lower than other respiratory infectious diseases.

Because mycoplasma is rarer than viruses and has a lower transmission capacity, outpatient and emergency department tests for patients with respiratory tract infections should focus on common viruses and bacteria, such as throat swabs for streptococci, urine antigens for Legionella, and especially nasal swabs for common respiratory viruses. However, these are not routine items in many outpatient and emergency departments in China.

This detection bias, coupled with the long-standing inertia of thinking and the profit-driven use of antibiotics after diagnosing mycoplasma infection, has made overdiagnosis and overtreatment a habit, and people still do it even if they know it is unreliable. In the past, many respiratory viral infections were treated as mycoplasma infections, and this possibility is not ruled out this time. Although for most patients, the outcome may not be much different, because most mycoplasma infections and viral infections can heal themselves with a good outcome. However, large-scale overtreatment may lead to a concentrated outbreak of adverse reactions - everyone is familiar with the consequences of the abuse of antibiotics, and there have been media reports of deaths caused by azithromycin.

Suspicion about the "epidemic" of mycoplasma infection also comes from a horizontal comparison with other parts of the world. A study published in The Lancet (Microbiology) in June this year tracked the prevalence of other respiratory infectious diseases during the COVID-19 pandemic.

In the early stages of the epidemic, due to various isolation measures, the incidence of many common respiratory infectious diseases unexpectedly dropped sharply, including mycoplasma infection. The proportion of patients with respiratory diseases who tested positive for mycoplasma (the positive rate of mycoplasma infection detected using direct detection methods including nucleic acid and antigen testing) dropped from 8.61% before the epidemic (2017-2020) to 1.69% (2020-2021).

A strange phenomenon occurred during the period of 2021-2022. Due to the relaxation of epidemic prevention measures in some places, other infectious diseases rebounded, including rhinovirus, influenza virus, respiratory syncytial virus, etc., but mycoplasma infection further dropped to 0.7%. Taking the University Children's Hospital of Zurich, Switzerland as an example, from April 2021 to March 2022, the number of positive samples of the new coronavirus sent for inspection was far ahead, reaching more than 5,000. Next was respiratory syncytial virus with 671 samples, rhinovirus with 523 samples, and other common respiratory viruses with more than 100 or double digits, but the number of positive mycoplasma was 0.

The above discovery attracted international attention, and the monitoring sites were expanded to 42 regions in 23 countries. Until March 2023, mycoplasma infection seemed to have disappeared. Among the more than 200,000 samples sent for testing, only more than 200 were positive, with a positive rate of only one in a thousand.

Nowadays, countries in the northern hemisphere have basically entered the peak period of respiratory infections. When searching for international news about the prevalence of mycoplasma, only the Global Times (English version) can be found. Compared with the high attention paid to mycoplasma in China, mycoplasma seems to be non-existent in other places.

We may have to wait and see who is wrong. We cannot rule out the possibility of mycoplasma resurgence around the world in the next few months. However, based on the reality of overdiagnosis and treatment of mycoplasma infection in the past, some verification and correction work is urgently needed before the current mycoplasma "epidemic" is identified, including:

Limit or cancel routine serological mycoplasma antibody testing for respiratory patients, and use nasal swab antigen testing instead for patients suspected of mycoplasma infection;

Promote respiratory virus-related testing;

Medical institutions and health management departments shall compile statistics on respiratory infection pathogens and publish them in a timely manner.

At present, domestic media and self-media have taken the mycoplasma outbreak as an established fact, but this result is very questionable. Accepting it without question may lead to repeated mistakes.

This article is supported by the Science Popularization China Starry Sky Project

Produced by: China Association for Science and Technology Department of Science Popularization

Producer: China Science and Technology Press Co., Ltd., Beijing Zhongke Xinghe Culture Media Co., Ltd.

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