Impact of immune checkpoint molecules on FoxP3+ Treg cells and related cytokines in patients with acute and chronic brucellosis.

BACKGROUND: The immunoregulatory functions of regulatory T cells (Tregs) in the development and progression of some chronic infectious diseases are mediated by immune checkpoint molecules and immunosuppressive cytokines. However, little is known about the immunosuppressive functions of Tregs in human brucellosis, which is a major burden in low-income countries. In this study, expressions of immune checkpoint molecules and Treg-related cytokines in patients with acute and chronic Brucella infection were evaluated to explore their impact at different stages of infection. METHODS: Forty patients with acute brucellosis and 19 patients with chronic brucellosis admitted to the Third People's Hospital of Linfen in Shanxi Province between August 2016 and November 2017 were enrolled. Serum and peripheral blood mononuclear cells were isolated from patients before antibiotic treatment and from 30 healthy subjects. The frequency of Tregs (CD4+ CD25+ FoxP3+ T cells) and expression of CTLA-4, GITR, and PD-1 on Treg cells were detected by flow cytometry. Levels of Treg-related cytokines, including IL-35, TGF-ß1, and IL-10, were measured by customised multiplex cytokine assays using the Luminex platform. RESULTS: The frequency of Tregs was higher in chronic patients than in healthy controls (P = 0.026) and acute patients (P = 0.042); The frequency of CTLA-4+ Tregs in chronic patients was significantly higher than that in healthy controls (P = 0.011). The frequencies of GITR+ and PD-1+ Tregs were significantly higher in acute and chronic patients than in healthy controls (P < 0.05), with no significant difference between the acute and chronic groups (all P > 0.05). Serum TGF-ß1 levels were higher in chronic patients (P = 0.029) and serum IL-10 levels were higher in acute patients (P = 0.033) than in healthy controls. We detected weak correlations between serum TGF-ß1 levels and the frequencies of Tregs (R = 0.309, P = 0.031) and CTLA-4+ Tregs (R = 0.302, P = 0.035). CONCLUSIONS: Treg cell immunity is involved in the chronicity of Brucella infection and indicates the implication of Tregs in the prognosis of brucellosis. CTLA-4 and TGF-ß1 may contribute to Tregs-mediated immunosuppression in the chronic infection stage of a Brucella infection.

Diagnosis, treatment, and prevention of monkeypox in children: an experts' consensus statement.

Monkeypox is a zoonotic disease. Since the first human monkeypox case was detected in 1970, it has been prevalent in some countries in central and western Africa. Since May 2022, monkeypox cases have been reported in more than 96 non-endemic countries and regions worldwide. As of September 14, 2022, there have been more than 58,200 human monkeypox cases, and there is community transmission. The cessation of smallpox vaccination in 1980, which had some cross-protection with monkeypox, resulted in a general lack of immunity to monkeypox, which caused global concern and vigilance. As of September 14, 2022, there are four monkeypox cases in China, including three in Taiwan province and one in Hong Kong city. Previous foreign studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications. In order to improve pediatricians' understanding of monkeypox and achieve early detection, early diagnosis, early treatment,  and early disposal, we have organized national authoritative experts in pediatric infection, respiratory, dermatology, critical care medicine, infectious diseases, and public health and others to formulate this expert consensus, on the basis of the latest "Clinical management and infection prevention and control for monkeypox" released by The World Health Organization, the "guidelines for diagnosis and treatment of monkeypox (version 2022)" issued by National Health Commission of the People's Republic of China and other relevant documents. During the development of this consensus, multidisciplinary experts have repeatedly demonstrated the etiology, epidemiology, transmission, clinical manifestations, laboratory examinations, diagnosis, differential diagnosis, treatment, discharge criteria, prevention, disposal process, and key points of prevention and control of suspected and confirmed cases.

[Clinical features, diagnosis and treatment of 5 cases of primary pneumonic plague in Tibet in 2010].

OBJECTIVE: To explore the clinical manifestations, the feature of chest X-ray, the clinical outcome, and the clinical treatments of severe pneumonic plague. METHODS: We observed the clinical course of primary pneumonic plague in 5 patients, who infected Yersinia pestis in Tibet during September 2010, including manifestations of chest X-ray, the antibiotic therapy, respiratory support and the prognosis. RESULTS: All of the 5 patients presented with high fever, bloody sputum and difficulty breathing. The chest X-ray showed signs consistent with necrotizing inflammation with multiple lobar involvement. Mass-like lesions might coalesce, and the "white lung" sign might appear. Three out of the 5 patients presented with hypoxemia. The results of reverse indirect hemagglutination assay (RIHA) in these patients were positive on the second day of the illness onset. All of these patients recovered after antibiotic therapy and other treatments. However, the absorption of lung lesions was very slow. CONCLUSIONS: Patients infected with primary pneumonic plague presented with rapid onset high fever and hemoptysis, and the lung injury was very severe. The positive result of RIHA was useful for early diagnosis of plague. Streptomycin should be the first choice for Yersinia pestis infection, but its optimal dose needed further study. Fluoroquinolones can be used as combination with Streptomycin. Nutritional support and symptomatic treatment, as well as non-invasive or invasive mechanical ventilation when needed, were important for the management of the disease.

[The analysis of the clinical features between survivors and non-survivors with the severe form of new influenza A (H1N1) viral infection].

OBJECTIVE: To understand the clinical features of critically ill patients with pandemic 2009 influenza A (H1N1) and investigate the risk factors associated with death cases. METHODS: The clinical features of 55 critically ill patients with pandemic 2009 influenza A (H1N1) viral infection hospitalized at Beijing Ditan Hospital from October 3 to December 15, 2009 were retrospectively analyzed, and a comparative analysis was performed on the manifestations of the survival and the death groups of patients. RESULTS: There were 31 males and 24 females. The age ranged from 10 months to 84 year old, and the mean (SD) was 38 (20) year old. The critically ill cases were more in patients under age 65 (48/55), with obesity (33/49), with underlying diseases (26/49), and pregnancy (6/24). Both the survivors and non-survivors of patients had high fever, cough, sputum (some sputum with blood), dyspnea, räles of both lungs fields, and all further developed severe pneumonia. The patients also showed respiratory failure (54/55) and ARDS (26/55). All of them received oseltamivir therapy, and 38 patients received mechanical ventilation and 30 were given steroid therapy. Secondary infection occurred in 27 cases, and ventilator-associated pneumonia happened in 10 patients. In the early stage of onset, C-reactive protein (CRP) increased [(131 ± 130) mg/L] and low counts of T lymphocytes were present [CD(4)(+), CD(8)(+) T was (217 ± 139)/µl and (162 ± 82)/µl]. With the progress of disease, the non-survival cases had persistently increased CRP and the counts of T lymphocytes did not recover, while the secondary fungal infection was significantly higher than in the survivor cases (P < 0.05). By using BMI, underlying diseases, ARDS, the day of Oseltamivir initiated, steroid therapy, following bacterial and fungal infection as variables through logistic regression analysis, it was shown that higher BMI and following fungal infection were associated with higher fatal risks (OR was 6.512, 19.631 respectively, both of P value was low than 0.05). There was no death case who received oseltamivir treatment within 48 hours of onset of disease. CONCLUSIONS: Critical illness in pandemic 2009 influenza A (H1N1) was associated with patients under age 65, with obesity, underlying diseases, and pregnancy. Persistently increased CRP and lower counts of T lymphocytes were associated with unfavorable prognosis. The patients with higher BMI and secondary fungal infection had higher fatal risks. Oseltamivir treatments at early stage would probably reduce mortality.

Clinical features of pediatric patients with COVID-19: a report of two family cluster cases.

BACKGROUND: Coronovirus disease 2019 (COVID-19) has spread rapidly across the globe. People of all ages are susceptible to COVID-19. However, literature reports on pediatric patients are limited. METHODS: To improve the recognition of COVID-19 infection in children, we retrospectively reviewed two confirmed pediatric cases from two family clusters. Both clinical features and laboratory examination results of the children and their family members were described. RESULTS: The two confirmed children only presented with mild respiratory or gastrointestinal symptoms. Both of them had normal chest CT images. After general and symptomatic treatments, both children recovered quickly. Both families had travel histories to Hubei Province. CONCLUSIONS: Pediatric patients with COVID-19 are mostly owing to family cluster or with a close contact history. Infected children have relatively milder clinical symptoms than infected adults. We should attach importance to early recognition, early diagnosis, and early treatment of infected children.

Soluble IL-2Rα correlates with imbalances of Th1/Th2 and Tc1/Tc2 cells in patients with acute brucellosis.

BACKGROUND: Previous studies showed that soluble IL-2Rα is an important marker of cellular immune activation and might be a marker of treatment efficacy for children with brucellosis. However, data regarding adult patients with brucellosis were unknown. The aim of study was to explore the potential role of serum sIL-2Rα evaluating treatment responses in adult patients with brucellosis, and T cell immune status was also examined. METHODS: During January 2016-April 2017, 30 patients with acute brucellosis from the Third People's Hospital of Linfen in Shanxi Province and Beijing Di Tan Hospital, and 28 healthy controls were included in this study. Peripheral blood samples were collected before and after six weeks of antibiotic treatment. Serum sIL-2Rα levels were measured by enzyme-linked immunosorbent assay, and the percentage of Th1, Th2, Tc1, Tc2, and Tregs was detected by flow cytometry after intracellular staining for cytokines (interferon-γ and interleukin-4) and Foxp3 in T lymphocytes from peripheral blood. The obtained data were analyzed with Wilcoxon ranked sum tests for paired values, Mann-Whitney U-tests for comparisons between patients and healthy controls, and Spearman rank tests for correlation analyses. RESULTS: Serum sIL-2Rα levels were significantly higher in patients than in controls (P = 0.001). A significant decline was observed in patients after the cessation of treatment (P < 0.001) and return to normal (P > 0.05). Th1, Tc1, Th2, and Tc2 cell frequencies were higher in patients than in healthy subjects (P < 0.05), while the Th1/Th2 and Tc1/Tc2 ratios were significantly lower (P = 0.0305 and 0.0005, respectively) and returned to normal levels after treatment. In patients with acute brucellosis, serum sIL-2Rα levels were negatively correlated with the Th1/Th2 ratio (r = - 0.478, P = 0.028), Tc1/Tc2 ratio (r = - 0.677, P = 0.001), and Tc1 percentage (r = - 0.516, P = 0.017). Serum sIL-2Rα and Tc2 percentages were positively correlated (r = 0.442, P = 0.045). CONCLUSIONS: Based on the correlations with Th1/Th2 and Tc1/Tc2 ratios, serum sIL-2Rα levels may reflect the immune response status. sIL-2Rα may be a marker for therapeutic efficacy in acute brucellosis.

Diagnosis and treatment of herpangina: Chinese expert consensus.

BACKGROUND: Herpangina is a common infectious disease in childhood caused by an enterovirus. This consensus is aiming to standardize and improve herpangina prevention and clinical diagnosis. METHODS: The Subspecialty Group of Infectious Diseases, the Society of Pediatric, Chinese Medical Association and Nation Medical Quality Control Center for Infectious Diseases gathered 20 experts to develop the consensus, who are specialized in diagnosis and treatment of herpangina. RESULTS: The main pathogenic serotypes of herpangina include Coxsackievirus-A, Enterovirus-A and Echovirus. Its diagnosis can be rendered on the basis of history of epidemiology, typical symptoms, characteristic pharyngeal damage and virological tests. The treatment is mainly symptomatic, and incorporates topical oral spray with antiviral drugs. The course of herpangina generally lasts 4-6 days with a good prognosis. CONCLUSION: The consensus could provide advices and references for the diagnosis, treatment and management of herpangina in children.

Updated diagnosis, treatment and prevention of COVID-19 in children: experts' consensus statement (condensed version of the second edition).

In the early February, 2020, we called up an experts' committee with more than 30 Chinese experts from 11 national medical academic organizations to formulate the first edition of consensus statement on diagnosis, treatment and prevention of coronavirus disease 2019 (COVID-19) in children, which has been published in this journal. With accumulated experiences in the diagnosis and treatment of COVID-19 in children, we have updated the consensus statement and released the second edition recently. The current version in English is a condensed version of the second edition of consensus statement on diagnosis, treatment and prevention of COVID-19 in children. In the current version, diagnosis and treatement criteria have been optimized, and early identification of severe and critical cases is highlighted. The early warning indicators for severe pediatric cases have been summarized which is utmost important for clinical practice. This version of experts consensus will be valuable for better prevention, diagnosis and treatment of COVID-19 in children worldwide.

Chinese guidelines for the diagnosis and treatment of hand, foot and mouth disease (2018 edition).

BACKGROUND: Hand, foot, and mouth disease (HFMD) is a common infectious disease in childhood caused by an enterovirus (EV), and which is principally seen in children under 5 years of age. To promote diagnostic awareness and effective treatments, to further standardize and strengthen the clinical management and to reduce the mortality of HFMD, the guidelines for diagnosis and treatment have been developed. METHODS: National Health Commission of China assembled an expert committee for a revision of the guidelines. The committee included 33 members who are specialized in diagnosis and treatment of HFMD. RESULTS: Early recognition of severe cases is utmost important in diagnosis and treatment of patients with HFMD. The key to diagnosis and treatment of severe cases lies in the timely and accurate recognition of stages 2 and 3 of HFMD, in order to stop progression to stage 4. Clinicians should particularly pay attention to those EV-A71 cases in children aged less than 3 years, and those with disease duration less than 3 days. The following indicators should alert the clinician of possible deterioration and impending critical disease: (1) persistent hyperthermia; (2) involvement of nervous system; (3) worsening respiratory rate and rhythm; (4) circulatory dysfunction; (5) elevated peripheral WBC count; (6) elevated blood glucose and (7) elevated blood lactic acid. For treatment, most mild cases can be treated as outpatients. Patients should be isolated to avoid cross-infection. Intense treatment modalities should be given for those severe cases. CONCLUSION: The guidelines can provide systematic guidance on the diagnosis and management of HFMD.

A practical community-based response strategy to interrupt Ebola transmission in sierra Leone, 2014-2015.

BACKGROUND: The Ebola virus disease spread rapidly in West Africa in 2014, leading to the loss of thousands of lives. Community engagement was one of the key strategies to interrupt Ebola transmission, and practical community level measures needed to be explored in the field and tailored to the specific context of communities. METHODS: First, community-level education on Ebola virus disease (EVD) prevention was launched for the community's social mobilizers in six districts in Sierra Leone beginning in November 2014. Then, from January to May of 2015, in three pilot communities, local trained community members were organized to engage in implementation of EVD prevention and transmission interruption measures, by involving them in alert case report, contact tracing, and social mobilization. The epidemiological indicators of transmission interruption in three study communities were evaluated. RESULTS: A total of 6 016 community social mobilizers from 185 wards were trained by holding 279 workshops in the six districts, and EVD message reached an estimated 631 680 residents. In three pilot communities, 72 EVD alert cases were reported, with 70.8 % of them detected by trained local community members, and 14 EVD cases were finally identified. Contact tracing detected 64.3 % of EVD cases. The median duration of community infectivity for the cases was 1 day. The secondary attack rate was 4.2 %, and no third generation of infection was triggered. No health worker was infected, and no unsafe burial and noncompliance to EVD control measures were recorded. The community-based measures were modeled to reduce 77 EVD cases, and the EVD-free goal was achieved four months earlier in study communities than whole country of Sierra Leone. CONCLUSIONS: The community-based strategy of social mobilization and community engagement was effective in case detection and reducing the extent of Ebola transmission in a country with weak health system. The successfully practical experience to reduce the risk of Ebola transmission in the community with poor resources would potentially be helpful for the global community to fight against the EVD and the other diseases in the future.

[Glucocorticoid in the treatment of severe acute respiratory syndrome patients: a preliminary report].

OBJECTIVE: To discuss the effect of glucocorticoid (methylprednisolone) on severe acute respiratory syndrome (SARS). METHODS: Thirty SARS patients were treated at our hospital for over 3 weeks since March to May 2003. The course and dosage of glucocorticoid, counts of CD(4)(+), CD(8)(+) and CD(3)(+), electrolytes, blood routine, and sera albumin before and after the treatment were analysed. RESULTS: Before treatment by methylprednisolone, the counts of CD(4)(+), CD(8)(+) and CD(3)(+) of 27 SARS patients were (401 +/- 203), (340 +/- 187), (756 +/- 383) cells/ microl. Twenty-nine of the 30 SARS patients were treated by methylprednisolone. The dosage for 24 patients was 80 - 160 mg/d with the largest being 1,000 mg/d before admission to the hospital. The count of WBC was increased after treatment (P < 0.01). No obvious effect was observed on the potassium, sodium and chlorine of blood (P > 0.05). Glucocorticoid increased the level of blood glucose (P = 0.01), decreased the level of sera albumin (P < 0.01), and its large dosage decreased the counts of CD(4)(+), CD(8)(+) and CD(3)(+). Three severe patients had secondary infection after administration of a large dose of glucocorticoid. CONCLUSIONS: In the early stage of the disease, the counts of CD(4)(+), CD(8)(+) and CD(3)(+) of SARS patients may reduce markedly indicating the immunity is suppressed. A large dose of glucocorticoid may aggravate the suppression and make the body in an active metabolic state (the increase of blood glucose and the decrease of sera albumin). Thus the disease is aggravated and patients are likely to suffer from severe secondary infection. Indications for use of glucocorticoid must strictly controlled and its large dosage is improper.

[Clinical analysis of SARS: 27 cases report].

OBJECTIVE: To realize the clinical characteristic of severe acute respiratory syndrome (SARS). METHODS: Observe the clinical signs and symptoms of each patients; do laboratory examination periodically; and at last do Stat analysis of all the cases. RESULTS: The first onset symptom of the 27 cases is high fever accompany with toxic symptom such as muscular soreness, headache, etc. The patient's condition may be most serious in the 2nd week. The amount of end-brush blood WBC decrease, especially the lymphocyte decrease more obviously. The amount of CD(4)(+) and CD(8)(+) decrease obviously is another important characteristic. The chest X-ray show pulmonary lesion in the 2nd day after onset of the illness, but 40.7% cases show positive change after 6 days onset. During the 7 - 12 days the pulmonary lesion become most serious. Seven cases are treated by steroid in the first 3 days when the chest X-ray is normal, but they become positive during 6 - 8 days of the course. Whether the state of the illness is serious or not seems no obvious relationship to when they are treated by steroid. And large dosage of steroid may inhibit the level of CD(4)(+) and CD8 (P < 0.05). Two severe cases present double infection after large dosage of steroid. CONCLUSION: The course of a infectious atypical pneumonia is almost 3 weeks, the 1st week can be decided as early stage, the 2nd week is decided as fastigium, the 3rd week is decided as stage of recovery. During the fastigium, the disease transform very quickly, we need pay more attention to the patient. The CD(4)(+), CD(8)(+) and CD(3)(+) of SARS patient decrease obviously, it seems the immuno-function inhibited seriously. The serious case is easily accompany with severe secondary infection in the late stage, so the use of steroid must be carefully and the dosage need not to be much more.