Comparison of the clinical characteristics in parents and their children in a series of family clustered Mycoplasma pneumoniae infections

Inclusion criteria: Patients who met the definition of familial cluster MP infection were included in the study. Familial cluster cases were defined as a situation where a minimum of two or more individuals from the same family were infected with MP, and the infection spanned across at least two generations. Infections among family members were classified as concurrent if they occurred within a 3-day period, and as sequential if they occurred within a 3 to 14-day period. The diagnostic criteria for Mycoplasma Pneumoniae Pneumonia (MPP) were as follows: Patients exhibited clinical symptoms indicative of a respiratory tract infection, such as fever, cough, and dyspnea. Radiological examinations revealed abnormalities in the chest. Additionally, the pathogenic test for MP yielded a positive result which was determined by any of the following: MP-IgM titers exceeding 1:160, a positive MP-DNA result, or the detection of MP through metagenomic next-generation sequencing. MP infection was defined as a positive MP result, in the absence of infiltrations on imaging. The diagnosis of adult severe Mycoplasma pneumoniae pneumonia (SMPP) was based on the 2016 Chinese guidelines for the diagnosis and treatment of adult community-acquired pneumonia [7]. Diagnosis of SMPP in children according to the Guidelines for the diagnosis and treatment of Mycoplasma pneumoniae pneumonia in children (2023 edition) [8].

Exclusion Criteria: Outpatients and inpatients who lacked access to complete information, such as records from hospitalizations at other institutions, were excluded from the study.

Assessing MP-specific IgM antibodies in plasma, with a titer of 1:160 or higher considered positive. Obtaining positive results from MP polymerase chain reaction (PCR) tests conducted on respiratory specimens. Detecting positive MP-DNA in bronchoalveolar lavage fluid using metagenomic next-generation sequencing. Macrolide-resistant Mycoplasma pneumoniae (MRMP) is detected by identifying specific single-nucleotide mutations in the V region of the 23S rRNA gene of the M. pneumoniae genome, which are indicative of macrolide resistance.

The study outcomes encompassed demographic attributes, results from laboratory tests, findings from lung imaging studies, outcomes of pathogen-specific laboratory tests, the status of treatments administered, and the treatment outcomes observed in both cohorts.

SPSS v26 software (IBM Statistics, Armonk, NY) was used for data analysis. Continuous data are expressed as mean ± standard deviation, with Student’s t-test. Categorical data are represented by the number of cases (%) for comparison of differences between groups using the non-parametric chi-squared test. A 2-sided alpha level of 0.05 was considered statistically significant.

We identified 63 family clusters of MP infection between August 2023 and October 2023, with one cluster involving three generations. These clusters comprised 87 adults and 69 children. In 41 (65.1%) families, the children were the first to be infected, followed by their parents who took care of them. In 15 (23.8%) families, the children were infected after the adults. Seven (11.1%) families had parents and children infected at the same time. Of these adults, 57 (65.5%) required hospitalization, 30 (34.5%) received outpatient or community care. Among the children, 65 (94.2%) were hospitalized (10 of them were admitted to another hospital and no data were available), and 4 (5.8%) were treated as outpatient. Finally, the parents group consisted of 57 patients (mean age 35.1 ± 4.6 years, 80.7% female) and the children group consisted of 55 patients (mean age 6.3 ± 3.9 years, 54.5% female) (Fig. 1).

Then, we observed a sharp increase in the incidence of mycoplasma infection in children after June 2023, reaching a peak of 69.1% in October 2023. In contrast, the incidence of mycoplasma infection in adults showed a gradual increase from October 2022 to October 2023, with a maximum of 18.2% in September (Supplemental Table 1 and Fig. 2).

The main symptoms at admission were fever, cough, and sputum production in both groups. The children group had a significantly higher proportion and peak of fever (39.1 ± 0.7 °C vs 38.6 ± 0.7 °C, p = 0.004) than the adults group. However, the adult group had a higher proportion of expectoration, headache and sore throat (Table 1).

On admission, only a small number of patients had moderately elevated leukocyte and neutrophil counts. Decreased lymphocyte count was more common in adults (25% vs 1.9%, p = 0.001). Thrombocytosis was more common in children group (37.0% vs 10.7%, p = 0.001), and no thrombocytopenia was observed in both groups. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were increased in most patients, but procalcitonin (PCT) increased more in children (76.9% vs 13.5%, p < 0.001). Prothrombin time (PT) was slightly prolonged in a few adults, and a minor increase in D-dimer levels was observed in a small fraction of patients in both groups. Liver dysfunction was mild, with elevated liver enzymes and bilirubin in adults, elevated aspartate aminotransferase (AST) and normal bilirubin in children. Only 3 adults had mild elevated creatine, and there was no renal impairment in children. Adults had a higher incidence of hypoalbuminemia (31.6% vs 11.1%, p = 0.009), but the albumin levels were only marginally lower. Lactate dehydrogenase (LDH) was increased in most children (42, 77.8%) and a few adults (6, 11.3%) (p < 0.001) (Table 2).

A total of 51 (89.5%) adults and 46 (88.5%) children were diagnosed with MPP. Patchy opacities on chest X-ray and computed tomography (CT) were the most frequent findings in both groups, affecting 47 (82.5%) adults and 44 (88%) children. Bronchial wall thickening was more prevalent in children (88% vs 40.4%, p < 0.001). Six adults and 11 children had consolidation and 3 had pleural effusion in both groups. Children tended to have bilateral pneumonia and adults tended to have unilateral pneumonia (Table 3). Figure 3 illustrates the typical CT findings of the four groups of family clusters of cases in this study.

MRMP was detected in 3 (60%) adults and 21 (52.5%) children. Co-infection was more prevalent in children than in adults (65.5% vs 22.8%, p < 0.001), with viral co-infection being the most frequent (41.8% in children). Other bacterial infections were detected in 3 (5.3%) adults and 20 (36.4%) children. Two adults and 3 children had fungal infection (Table 4).

The antibiotic regimens varied between the two groups in some aspects. Macrolides were used in most children (96.4% vs 14.0%, p < 0.001) and quinolones were used in most adults (96.5% vs 3.6%, p < 0.001). Tetracyclines were used in 14 (25.5%) children. More children than adults switched from macrolides to alternative therapy (34.5% vs 7.0%, p < 0.001). Five children with MRMP infection changed from azithromycin to clindamycin, with good treatment effects. Besides antibiotic regimens, the two groups received different treatments. Glucocorticoids were given to 36 (65.5%) children and 5 (8.8%) adults, p < 0.001. Two children (3.6%) received immunoglobulin therapy, while none of the parents did.

Only one child with MRMP required intensive care unit (ICU) admission, where he received oxygen therapy, corticosteroids, intravenous immunoglobulin, meropenem and eventually had a good outcome. Children had a significantly longer fever duration than adults ((5.6 ± 2.2) days vs (4.1 ± 2.2) days, p = 0.002). None of the adults had SMPP, while 10 children (18.2%) fulfilled the diagnostic criteria for SMPP. No patients in this study required mechanical ventilation or died (Table 5).