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Mycoplasma hyopneumoniae (M. hyopneumoniae) is the causal agent of mycoplasmal pneumonia (MP). MP is frequently complicated with other bacteria (enzootic pneumonia [EP]) and viruses (porcine respiratory disease complex [PRDC]), which affect the severity of the disease. These chronic respiratory infectious processes affect mainly growing and finishing pigs and are significant causes of economic losses to swine producers throughout the world .
An estimated 11 to 15% of U.S. laboratory cell cultures are contaminated with mycoplasma.A Corning study showed that half of U.S. scientists did not test for Mycoplasma contamination in their cell cultures. The study also stated that, in former Czechoslovakia, 100% of cell cultures that were not routinely tested were contaminated while only 2% of those routinely tested were contaminated (study p. 6). Since the U.S. contamination rate was based on a study of companies that routinely checked for Mycoplasma, the actual contamination rate may be higher. European contamination rates are higher and that of other countries are higher still (up to 80% of Japanese cell cultures).About 1% of published Gene Expression Omnibus data may have been compromised. Several antibiotic-containing formulations of antimycoplasmal reagents have been developed over the years.
The presence of Mycoplasma was first reported in samples of cancer tissue in the 1960s. Since then, several studies tried to find and prove the connection between Mycoplasma and cancer, as well as how the bacterium might be involved in the formation of cancer. Several studies have shown that cells that are chronically infected with the bacteria go through a multistep transformation. The changes caused by chronic mycoplasmal infections occur gradually and are both morphological and genetic. The first visual sign of infection is when the cells gradually shift from their normal form to sickle-shaped. They also become hyperchromatic due to an increase of DNA in the nucleus of the cells. In later stages, the cells lose the need for solid support to grow and proliferate, as well as the normal contact-dependent inhibition cells.
Mycoplasmal pneumonia is a category V infectious disease in the National Epidemiological Surveillance of Infectious Diseases (NESID) under the Law Concerning the Prevention of Infectious Diseases and Medical Care for Patients of Infections (the Infectious Diseases Control Law) enforced on April 1, 1999. Sentinel hospitals* regularly report the weekly number of mycoplasmal pneumonia patients (total of outpatients and inpatients). In addition to isolation of Mycoplasma pneumoniae or detection of serum antibody to M. pneumoniae, detection of M. pneumoniae genome by PCR or LAMP has been included in the notification criteria ( -kansenshou11/01-05-38.html) since its modification in April 2011. Recently, the reported number of mycoplasmal pneumonia patients is increasing (Fig. 1).
Periodicity of mycoplasmal pneumonia epidemics and the epidemic that started in 2011: Periodicity of mycoplasmal pneumonia epidemic at a 3-8 year interval has been observed worldwide. It is presumably brought about by the herd immunity vs. pathogen interaction but its exact mechanism is unknown. Seasonally, mycoplasmal pneumonia is prevalent from autumn to winter, and occasionally also in early summer (Fig. 1).
Age and geographical distribution of mycoplasmal pneumonia patients: Children aged 1-14 years occupied 80% of the patients. Among them, since 2011, age group 10-14 years increased and that below 4 years decreased in proportion (Fig. 2). As such age group shift has been observed in the past (IASR 28: 31-32, 2007), the present resurgence of mycoplasmal pneumonia may not be related to the age shift.
Regionally, since 2007, Aomori, Miyagi, Fukushima, Gunma, Saitama and Okinawa sentinel points have reported larger number of mycoplasmal pneumonia cases, and since 2010, Iwate, Tochigi, Toyama, Aichi, Gifu, Osaka, Ehime and Saga also do so (Fig. 3). Since 2011, other prefectures with fewer cases started to report larger number of cases than before.
Increase of macrolide resistance: Macrolide antibiotics are used for treatment of mycoplasmal pneumonia. However, since 2000 when the macrolide-resistant M. pneumoniae was first reported in Japan, macrolide-resistant strains are found continuously increasing in Asia and nearby regions (IASR 32: 337-339, 2011). Now, more than 50% of clinical isolates in Japan are estimated to be macrolide resistant (see pp. 264, 265 & 267 of this issue). However, European countries experiencing mycoplasmal pneumonia epidemic similarly as Japan report the macrolide resistance rate below 10%. Macrolide-resistant strains are more often isolated from pediatric patients rather than adults. Macrolide resistance itself does not significantly affect the sequel as most cases recover without chemotherapy. When the patients received chemotherapy, feverish phase may prolong in case of macrolide-resistant M. pneumoniae infection than in case of macrolide-susceptible one (IASR 28: 41-42, 2007 and see p. 266 of this issue). Macrolide-resistant M. pneumoniae infection can be effectively treated with quinolone and tetracycline antibiotics, and no resistant clinical isolates have been reported in the world including Japan. However, their use for children should be limited to really serious cases on account of their potential side effects (see p. 268 of this issue).
Laboratory diagnosis of mycoplasmal pneumonia: Culture, serodiagnosis and gene amplification methods are available. Isolation of M. pneumoniae is the most reliable, but 1-4 weeks are required for obtaining the final data. PA, EIA and other serodiagnostic kits are preferentially used in clinical settings for the rapid test. However, it is useful only when the paired serum antibody titers of the patients were obtained. The current most reliable rapid diagnosis is PCR, LAMP and other gene amplification methods (see p. 268 of this issue). LAMP method has been covered by the health insurance since October 2011.
Final Comments: The progressing mycoplasmal pneumonia epidemic in Japan ( -weeklygraph/1659-18myco.html) necessitates continued surveillance of patients and continued monitoring of drug-resistance and pathogenicity of the bacterial isolates.
Chlamydial or mycoplasmal infection is suspected in patients with symptoms of urethritis, salpingitis, cervicitis, or unexplained proctitis, but similar symptoms can also result from gonococcal infection.
Typically, mycoplasmal pneumonia is seen in pigs in the growing-finishing phase of production. Pigs exhibit a dry, nonproductive cough that may persist for 1 to 2 months. As the disease spreads from pig to pig in a group, the group may appear to have the disease until slaughter. Pigs infected with only M. hyopneumoniae have normal feed intakes and average daily gains. However, concurrent infection with secondary pathogens results in decreased feed intake, and consequently the pigs fail to grow at a normal rate. Variation in the number and identity of the secondary organisms, dose of M. hyopneumoniae organisms, and the extent of the pneumonia results in a variable depression of the growth rate in a group of infected pigs.
Clinical signs and lesions of mycoplasmal pneumonia are occasionally observed in nursery pigs in the presence of PRRSV and other secondary organisms. Pigs will exhibit fever, lethargy, respiratory distress, and decreased feed consumption. The percentage of pneumonia in these pigs can be extremely high with greater than 80% of the lungs of an individual pig showing lesions of pneumonia.
Although the specific economic effect of mycoplasmal pneumonia can be difficult to ascertain, a review of a number of studies of herds with enzootic pneumonia found a 17% decrease in daily weight gain and a 14% decrease in feed efficiency. In addition, it has been estimated that for every 10% of the lung with pneumonia, the mean daily gain is reduced by 37 grams. One study estimated that the cost per pig for mycoplasmal pneumonia was $4.08, and the annual cost for the entire U.S. swine industry was about $367 million. This cost excluded the costs of drugs used to treat or reduce the effects of this disease (which has been estimated to be around $100 million) and the disease-enhancing effects of poor management.
Diagnosis of mycoplasmal pneumonia remains difficult. Currently, the best results are achieved by clinical observation, postmortem and histological examinations, and fluorescent antibody examination. Polymerase chain reaction (PCR) assays are increasing in popularity. Expense, environmental contamination, and proper sample collection and handling all must be considered when using PCR for diagnostic purposes. Isolation of M. hyopneumoniae organisms is slow, difficult, and not routinely available. In addition, the laboratory isolating the organism must be able to differentiate M. hyopneumoniae from other common non-disease inducing species of mycoplasmas. Enzyme linked immuno-sorbent assay (ELISA) is the primary test used for measuring antibodies in serum. Several types of ELISA assays are available, so interpretation is test specific. ELISA results can aid in supporting a diagnosis of M. hyopneumoniae infection in a herd. However, depending on the ELISA test used, antibodies can be detected in the serum within 2 to 6 weeks of exposure of infected animals, making use of serology a poor measure of timing of infection.
Antibiotics. Antibiotics are frequently used to treat pneumonia in pigs. Many antibiotics appear to be effective against M. hyopneumoniae in the laboratory. However, their success in the pig is often poor. A recent study found that chlortetracycline administered prior to infection was effective in decreasing both the formation of pneumonia and the number of organisms. Administration of the drug following infection resulted in no reduction in pneumonia; however, the numb