2000--2013年沧州市健康人群流行性脑脊髓膜炎带菌监测结果

目的了解沧州市2000--2013年的健康人群流行性脑脊髓膜炎（简称流脑）带菌率和菌型分布变迁状况,为提出新的免疫策略,制定有效的防控措施,控制暴发提供依据。方法每年在流脑流行前期（12月至1月）、流行期（3月）和流行后期（5月）,采用分层随机抽样方法,采集0～6、7～12、13～17和18岁以上4个不同年龄组的咽拭子标本,进行健康人群流脑带菌调查和分析。依据WS295-2008《流行性脑脊髓膜炎诊断标准》进行脑膜炎奈瑟菌分离培养和鉴定,数据用SPSS17．0软件包统计分析。结果2000--2013年连续14年监测的4865人中,检出带菌者232人,总带菌率为4．77％。其中2000和2003年带菌率最高,为9．09％;2013年最低,为0．42％。共检出流脑菌群11群,分别为A、B、C、D、X、Y、29E、W135、H、I和K群。其中以B群检出率最高,为1．19％;其次Y群,为1．09％,A和c群的检出率分别为0．60％和0．25％;检出率最低的是W135群（0．14％）。13～17岁组带菌率最高,为6．63％;其次是0～6和7—12岁组,分别为4．10％和4．06％;最低的是18岁以上组,为3．09％。4个年龄组带菌率比较,差异有统计学意义（χ2=20．83,P〈0．01）。结论连续14年的监测结果表明,沧州市健康人群流脑带菌率呈现下降趋势,特别是2008年以后下降更为明显,反映了多年来沧州市对流脑监测和疫苗接种工作的重视。13—17岁组带菌率最高,提示今后要加强该年龄组人群的监测、预防接种以及健康教育工作。带菌者中检出了致病菌株,且检出率高于其他菌群,提示今后A＋C流脑疫苗仍应在沧州市继续推广应用。     

济南市2011年急性脑膜炎/脑炎症候群病例哨点监测分析

目的了解济南市2011年急性脑膜炎/脑炎症候群（Acute Meningitis/Encephalitis Syndrome,AMES）哨点监测病例的主要病毒性病原及其流行病学特征。方法在济南市选取省、市、县级各2所医院作为哨点医院,收集2011年AMES病例血清和脑脊液（Cerebrospinal Fluid,CSF）标本,采用酶联免疫吸附试验对4种病毒特异性免疫球蛋白（Immunoglobilin,Ig）M进行血清学诊断。结果济南市2011年报告的AMES病例集中在5-9月,高峰出现在6-8月,峰值出现在7月,但≥15岁的病例数无季节性高峰。所有病例的血清和CSF标本均检测了流行性乙型脑炎病毒（Japanese Encephalitis Virus,JEV）IgM,阳性率为7.1%（46/647例）,比2008-2010年明显下降,其差异有统计学意义（χ2=12.6,P〈0.05）。其余血清标本IgM检测结果为：人类肠道病毒（Human Enterovirus,HEV）阳性率为18.5%（61/330例）,流行性腮腺炎病毒（Mumps Virus,MuV）阳性率为13.9%（46/330例）,单纯疱疹病毒（Herpes Simplex Virus,HSV）阳性率为13.0%（43/330例）。不同年龄组病例的主要病原存在差异,〈5岁以HEV感染为主,而≥15岁则以HSV为主。与其他3种病毒的季节分布不同,MuV感染全年无明显差异（χ2=5.4,P=0.36）。4种病毒中,仅HSV感染有明显的性别差异（χ2=5.1,P=0.02）,女性感染较多。结论济南市2011年6所哨点医院AMES病例的主要病毒性病原体依次为HEV、MuV、HSV、JEV。由于不同病毒的流行病学特征不同,需针对病毒的特性制定个性化监测方案,并加强实验室检测。     

Inhibitory effect of icariin on Ti-induced inflammatory osteoclastogenesis

Background

Wear particle-induced periprosthetic osteolysis that results in aseptic loosening is the most common cause of long-term failure after total joint replacement.

Materials and methods

Icariin (ICA), a flavonoid isolated from Epimedium pubescens, inhibits osteoclast formation, but its effects on wear particle-induced inflammatory osteoclastogenesis remains unclear. We investigated the role of ICA in the regulation of osteoclast differentiation in a murine macrophage cell line (RAW264.7), which is stimulated by titanium (Ti) particles and the receptor activator of NF-κB ligand.

Results

ICA effectively inhibited osteoclast formation and bone resorption in the differentiation medium. ICA (10⁻⁷ mol/L) significantly reduced the number of tartrate-resistant acid phosphatase-positive cells compared with the control, and significantly reduced the percentage of the surface covered by resorption lacunae. Quantitative real-time polymerase chain reaction analysis showed that ICA inhibited messenger RNA expression for the receptor activator of nuclear factor-κB, cathepsin K, tartrate-resistant acid phosphatase-positive, and matrix metalloproteinase-9 in RAW264.7 cells stimulated by Ti particles and receptor activator of NF-κB ligand. ICA also reduced pro-inflammatory cytokine expression of interleukin-1β and tumor necrosis factor-α in RAW264.7 cells cultured with Ti particles. In addition, incubation with cholecystokinin-8 showed that ICA had no toxic effects on RAW264.7 cells.

Conclusions

ICA possibly elicited inhibitory effects on inflammatory osteoclastogenesis induced by Ti particles, indicating that ICA may be useful for the prevention and treatment of wear particle-induced osteolysis.     

中枢神经系统感染患儿血清、脑脊液 MMP-9和 IL-1β水平变化及意义

目的：观察中枢神经系统感染患儿血清、脑脊液基质金属蛋白酶9（MMP-9）和IL-1β水平变化,并探讨其意义。方法急性期中枢神经系统感染患儿50例,其中化脓性脑膜炎20例（化脑组）、病毒性脑炎30例（病脑组）,非中枢神经系统感染患儿30例（对照组）,采用ELISA法检测各组患儿血清及脑脊液MMP-9、IL-1β,全自动生化分析仪检测血清白蛋白（SAlb）,免疫比浊法检测脑脊液白蛋白（CAlb）,计算白蛋白指数（AQ）。结果化脑组、病脑组、对照组血清MMP-9水平分别为（489．98±159．09）、（267．85±91．89）、（133．03±31．64）μg/L,血清IL-1β水平分别为（21．35±4．91）、（19．57±5．70）、（14．07±3．94） ng/L,脑脊液MMP-9水平分别为（116．8±41．78）、（37．19±17．87）、（10．25±5．33）μg/L,脑脊液IL-1β水平分别为（106．28±12．83）、（66．95±10．63）、（49．97±12．57）ng/L,化脑组、病脑组分别与对照组比较,P均＜0．01;化脑组与病脑组比较,P均＜0．01（除血清IL-1β水平外）。化脑组、病脑组、对照组SAlb水平分别为（38．75±2．73）、（39．57±3．95）、（39．37±4．14） g/L,三组比较,P＞0．01;CAlb水平分别为（1．04±0．28）、（0．54±0．14）、（0．18±0．08）g/L,AQ分别为26．97±7．29、13．76±3．45、4．61±2．05,化脑组、病脑组分别与对照组比较,P均＜0．01;化脑组与病脑组比较,P均＜0．01。化脑组、病脑组血清MMP-9、IL-1β水平呈正相关（r＝0．304,P均＜0．05）,脑脊液MMP-9、IL-1β水平呈正相关（r＝0．834,P＜0．05）。结论中枢神经系统感染患儿血清、脑脊液MMP-9、IL-1β、CAlb水平升高,AQ增加,MMP-9、IL-1β可能参与了中枢神经系统感染血-脑脊液屏障功能损伤的病理过程。     

Preclinical immunogenicity study of trivalent meningococcal AWX-OMV vaccines for the African meningitis belt

In the recent decade, epidemic meningitis in the African meningitis belt has mostly been caused by Neisseria meningitidis of serogroups A, W and X (MenA, MenW and MenX, respectively). There is at present no licensed vaccine available to prevent MenX meningococcal disease. To explore a trivalent MenAWX vaccine concept, we have studied the immunogenicity in mice of MenX outer membrane vesicles (X-OMV) or MenX polysaccharide (X-PS) when combined with a bivalent A-OMV and W-OMV (AW-OMV) vaccine previously shown to be highly immunogenic in mice. The vaccine antigens were produced from three representative wild type strains of MenA (ST-7), MenW (ST-11) and MenX (ST-751) isolated from patients in the African meningitis belt. Groups of mice were immunized with two doses of X-OMV or X-PS combined with the AW-OMV vaccine or as individual components. All vaccine preparations were adsorbed to Al(OH)₃. Sera from immunized mice were tested by ELISA and immunoblotting. Functional antibody responses were measured as serum bactericidal activity (SBA) and opsonophagocytic activity (OPA). Immunization of mice with X-OMV, alone or in combination with AW-OMV induced high levels of anti-X OMV IgG. Moreover, X-OMV alone or in combination with the AW-OMV vaccine induced high SBA and OPA titers against the MenX target strain. X-PS alone was not immunogenic in mice; however, addition of the AW-OMV vaccine to X-PS increased the immunogenicity of X-PS. Both AWX vaccine formulations induced high levels of IgG against A- and W-OMV and high SBA titers against the MenA and MenW vaccine strains. These results suggest that a trivalent AWX vaccine, either as a combination of OMV or OMV with X-PS, could potentially prevent the majority of meningococcal disease in the meningitis belt.     

Cryptococcal meningitis with atypical paradoxical inflammatory reactions after antifungal treatment in acquired immune deficiency syndrome: A case report

Cryptococcal meningitis (CM) is a life-threatening disease that primarily affects patients with human immunodeficiency virus (HIV). Antifungal therapy with antiretroviral treatment (ART) usually leads to the clinical remission of CM; however, in some cases, these treatments exacerbate intracranial inflammation because of paradoxical inflammatory reaction or immune reconstitution inflammatory syndrome (IRIS). Here we report two CM cases that presented atypical clinical courses attributed to paradoxical inflammatory reactions.The first case was a 43-year-old man with headache and vertigo diagnosed with CM and HIV. The patient's CM not only was refractory to the antifungal combination therapy of liposomal amphotericin B (L-AMB) and fluconazole (FLCZ) but suddenly worsened because of a paradoxical inflammatory reaction after 18 days of treatment. He passed away from brain herniation on day 23. The second case was a 43-year-old man diagnosed with CM and HIV. After receiving antifungal therapy and ART, the patient's status was stable for more than 3 years with undetectable HIV-RNA. He suddenly presented with brain inflammation and was diagnosed with IRIS due to CM (CM-IRIS). His brain lesions were migratory and refractory to various antifungal therapies such as L-AMB, FLCZ, flucytosine, and intrathecal amphotericin B. Although the cryptococcal antigen in the patient's cerebrospinal fluid gradually diminished after continuous antifungal therapies, his cognitive function declined, and right hemiparesis persisted.These two cases of CM presented atypical clinical courses, presumably because of paradoxical inflammatory reactions. It should be noted that the onset of CM-IRIS may not necessarily depend on the timing of ART initiation.     

Cryptococcal meningitis accompanying lymphocytic inflammation predominantly in cerebral deep white matter: A possible manifestation of immune reconstitution inflammatory syndrome

Cryptococcal meningitis is rarely complicated by immune‐mediated leukoencephalopathy, but the precise pathomechanism is uncertain. A 72‐year‐old Japanese man treated with prednisolone for Sweet disease developed a subacute progression of meningitis, which was considered as neuro‐Sweet disease. A treatment by methylprednisolone rapidly improved CSF findings with a remarkable decrease in lymphocyte numbers in the blood, but the patient's consciousness still worsened after the cessation of the treatment. The patient developed cryptococcal meningitis and MRI showed abnormal intensities predominantly in the cerebral deep white matter along with the recovery of lymphocyte numbers in the blood, which resulted in death. A postmortem examination of the brain revealed degenerative lesions, especially at the cerebral white matter and cortex adjacent to the leptomeninges abundantly infiltrated by Cryptococcus neoformans. In the affected cerebral deep white matter, perivascular infiltration of lymphocytes was prominent in coexistence with reactive astrocytes and vascular proliferation, but these findings were not observed in the subcortical and cortical lesions. Cryptococcus neoformans was not present within the brain parenchyma. This is the first report of a case suggesting that cryptococcal meningitis can accompany lymphocytic inflammation predominantly in cerebral deep white matter as a possible manifestation of immune reconstitution inflammatory syndrome.