Clinical Efficacy of Andrographolide Sulfonate in the Treatment of Severe Hand, Foot, and Mouth Disease (HFMD) is Dependent upon Inhibition of Neutrophil Activation.

Andrographolide sulfonate treatment has been shown to improve clinical severe hand, foot, and mouth disease (HFMD) efficacies when combined with conventional therapy. However, the mechanisms for its therapeutic effects remain elusive. In this study, we aimed to investigate whether andrographolide sulfonate exerts its efficacy by acting on neutrophil activation. We obtained serial plasma samples at two time points (before and after 5 days of therapy) from 28 HFMD patients who received conventional therapy and 18 patients who received combination therapy (andrographolide sulfonate plus conventional therapy). Then, we measured plasma myeloperoxidase (MPO), S100A8/A9, histone, and inflammatory cytokine levels. Furthermore, we examined if andrographolide sulfonate had direct effects on neutrophil activation in vitro. We observed that MPO and S100A8/A9 levels were markedly elevated in the HFMD patients before clinical treatment. At 5 days post-medication, the MPO, S100A8/A9, histone, and interleukin-6 levels were markedly lower in the combination therapy group compared with the conventional therapy group. In vitro studies showed that andrographolide sulfonate inhibited lipopolysaccharide-stimulated neutrophil activation, demonstrated by the decreased production of reactive oxygen species and cytokines. These data indicate that neutrophil activation modulation by andrographolide sulfonate may be a critical determinant for its clinical HFMD treatment efficacy. Copyright © 2015 John Wiley & Sons, Ltd.

Integrated analysis reveals important differences in the gut and oropharyngeal microbiota between children with mild and severe hand, foot, and mouth disease.

Little is known about alternation and difference in gut microbiota between patients with mild and severe hand, foot, and mouth disease (HFMD). We investigated the differences in gut and oropharynx microbiota between mild and severe HFMD in young children and changes in bacterial profiles as the disease progresses from acute to convalescent phase. Forty-two patients with confirmed HFMD were studied, among which 32 had severe HFMD and 10 had mild HFMD. First rectal swabs were collected from all patients at an average of 2 days (acute phase) after the onset of symptoms, and second rectal swabs were collected from 8 severe patients at day 9 (convalescent phase) after the onset. Oropharyngeal swabs were obtained from 10 patients in the acute phase and 6 in the convalescent phase. 16S rRNA sequencing was performed for all 70 samples. Compared with mild HFMD, severe HFMD exhibited significantly decreased diversity and richness of gut microbiota. Gut microbiota bacterial profiles observed in the acute and convalescent phases resembled each other but differed from those in mild cases. Additionally, 50% of patients with severe HFMD in the acute phase harboured a dominant pathobiontic bacterial genus. However, none of the patients with mild HFMD had such bacteria. Similar bacterial compositions in oropharynx microbiota were detected between mild and severe cases. Our findings indicate that severe HFMD exhibits significantly impaired diversity of gut microbiota and frequent gut and oropharyngeal inflammation-inducing bacteria. However, the results should be interpreted with caution as the number of subjects was limited.

A new factor influencing pathogen detection by molecular assay in children with both mild and severe hand, foot, and mouth disease.

This study aimed to find novel information concerning pathogen detection and some probable coinfection factors in hand, foot, and mouth disease (HFMD). In this study, 1104 clinically diagnosed HFMD patients were included. Enterovirus 71 (EV71), coxsackievirus A16 (CA16), and 14 different respiratory pathogens were examined from nasopharyngeal swabs using polymerase chain reaction (PCR) or reverse transcriptase PCR (RT-PCR). To evaluate the immune activation in HFMD patients, 8 cytokines and IgM antibodies to EV71 and CA16 from mild and severe patients were detected. Our results indicated that the severity of HFMD may affect the pathogen detection. The lower positive rates of enterovirus and respiratory viruses in severe HFMD cases by RT-PCR were probably related to stronger immune response. Therefore, immunological tests such as ELISA are essential supplements to PCR or RT-PCR in order to increase pathogen diagnosis in HFMD, especially in severe cases.