The reviewed paper [1] was a combined effort from John Hopkins University Center for Medical Research and Training and Institute of Child Health, Calcutta. It describes the clinical course of an Indian girl with pneumonitis which was subsequently diagnosed to be due to M. pneumoniae. It was only 4 years prior to this publication that M. pneumoniae was successfully cultivated in cell-free medium [2]. The investigations of this child were supported by United States Public health service research grant from National Institute of Health. The reported case was a 23-month old Bengali girl, eleventh in birth order! She presented with a seven day history of fever, coryza and progressive cough that was severe at night with a few instances of post-tussive vomiting. There was a past history of repeated upper respiratory tract infections. She was immunized only against small pox. Examination revealed fever, tachycardia and tachypnea. The child had cervical and axillary lymphadenopathy, hyperemia of nasal mucosa and tonsils, and an injected tympanic membrane. The chest was hyperinflated; the right lower chest was dull on percussion with diminished breath sound. Occasional inspiratory and expiratory rales were heard over the affected area. Cardiac examination was normal; the liver was palpable 5 cm and spleen 2 cm below costal margin. The chest X-ray demonstrated a confluent opacification of the right middle lobe consistent with alveolar pneumonitis and peribronchitis in the right upper and lower lobes. Blood counts showed a neutrophilic leukocytosis. Tuberculin skin test was negative and sweat chloride was normal.

Historical background and past knowledge: In the late nineteenth century, Nocard and Roux isolated the first mycoplasma organism from cattle suffering from pleuropneumonia [3]. This was followed by the discovery of other mycoplasma from various animal species, which were termed as pleuropneumonia like organisms (PPLO). The isolation of first human mycoplasma (Mycoplasma hominis) is credited to Dienes and Edsall [4] in 1937 from a Bartholin gland abscess. In 1944, Eaton and colleagues discovered an organism termed Eaton agent, as the cause of pneumonia [5]. This agent was considered a virus till 1961, when Marmion and Goodburn [6] described it to be morphologically similar to PPLO. Eventually in 1962, Chanock, et al. [2] described the Eaton agent to be a mycoplasma after its successful cultivation in cell-free media. Shortly thereafter, he proposed the name Mycoplasma pneumoniae as the organism inoculated in human volunteers produced pneumonia. Kingston, et al. [7] established the therapeutic efficacy of demethyl-tetracycline for M. pneumoniae pneumonia.

The organism was peculiarly known for causing cold agglutinin positive primary atypical pneumonia in military recruits and close population subgroups [8], but it was relatively uncommon in early childhood. The isolation of this organism was slow and difficult, serological tests were being developed and indistinctive clinical picture did not itself lead to the diagnosis.

A lot has been learnt about its biological properties since isolation of the organism in 1962. M. pneumoniae are now known to be the smallest free-living ubiquitous organisms. The pathogenicity in humans is attributed to the phenomena of cyto-adhesion at the mucosa of the respiratory epithelium, impaired muco-ciliary clearance and elaboration of a cytotoxin called as CARDS toxin that damages the respiratory ciliated epithelial cells. In addition, infection with M. pneumoniae induces production of pro-inflammatory mediators and cytokines, which further exacerbate the disease process. The ability of mycoplasma to internalize and replicate in alveolar macrophages can lead to chronicity of infection and resistance to antibiotics [9]. Recurrences are known to occur.

In contrast to the historic belief of occurrence of M. pneumoniae infection among closed populations groups like military bases and boarding schools, the infection and disease occurs throughout the year punctuated by cyclical epidemics which are specific to geographic locations. Pneumonia is the most important manifestation seen in children aged between 5 and 15 years, while wheezing occurs more commonly in under-five children. It is speculated to cause asthma exacerbations [10], and can lead to decreased pulmonary clearance and airway hyper-responsiveness even after the control of infection.

Even today, it is practically very difficult to diagnose M. pneumoniae infection. Culture techniques require specialized expertise, and are used only for research purposes for geno-typing and anti-microbial susceptibility testing. Serological tests require paired samples (acute and convalescent 2-3 weeks apart) for definitive diagnosis. The detection of mycoplasma using cold agglutination test is non-specific with limited diagnostic utility. The complement fixation test, which was considered standard diagnostic tool till 2 decades ago, has been replaced by rapid, single-specimen, specific antibody detection (IgM or IgA) against mycoplasma antigens using membrane-based enzyme-linked immunosorbent assays or immuno-flourescence. Specific IgM and IgA responses need to be combined with direct pathogen detection for establishing causation. Polymerase chain reaction (PCR) using numerous gene sequences of M. pneumoniae as primers is a highly sensitive and specific test to detect M. pneumoniae in various specimens like respiratory secretions, blood, CSF and urine, but lacks validation and standardization. In this setting, it is commendable that authors of this case record could make a diagnosis of M. pneumonia infection 50 years ago!

For treatment of M. pneumoniae infection, macrolides (azithromycin and clarithromycin) are now prefered in children. The children and adult contacts are advised to follow personal protective measures during period of infectivity till the index case continues to cough. The trials for the development of vaccines are underway, but still have a long way to go.

1. Hughes JR, Sinha DP. Mycoplasma pneumoniae infection in an Indian child. Indian Pediatr. 1966; 3:52-9.

2. Chanock RM, Hayflick L, Barile MF. Growth on artificial medium of an agent associated with atypical pneumonia and its identification as a PPLO. Proc Natl Acad Sci USA. 1962;48:41-9.

3. Nocard E, Roux ER. Le microbe de la pleuro-pneumoniae. Ann Inst Pasteur (Paris). 1898;12:240-62.

4. Dienes L, Edsall G. Observations on L-organisms of Klieneberger. Proc Soc Exp Biol Med. 1937;36:740-4.

5. Eaton MD, Meiklejohn G, Van Herick W. Studies on the etiology of primary atypical pneumonia: A filterable agent transmissible to cotton rats, hamsters, and chick embryos. J Exp Med. 1944;79:649-68.

6. Marmion BP, Goodburn GM. Effect of an organic gold salt on Eaton’s primary atypical pneumonia agent and other observations. Nature.1961;189:247-8.

7. Kingston JR, Chanock RM, Mufson MA Hellman LP, James WD, Fox HH, et al. Eaton agent pneumonia. JAMA.1961;176:118-23.

8. Chanock RM, Mufson M, Bloom HH, James WD, Fox HH, Kingston JR. Eaton agent pneumonia. JAMA.. 1961;175:213-20.

9. Dallo SF, Baseman JB. Intracellular DNA replication and long-term survival of pathogenic mycoplasma. Microb Pathogen. 2000;29:301-9.