我国类鼻疽病的流行病学特征及诊疗的研究进展

类鼻疽病是由类鼻疽伯克霍尔德菌(Burkholderia pseudomallei)感染引起的一类人畜共患病,主要流行于全球热带及亚热带地区。在我国主要流行于南部地区,疫源地为海南、广东、广西、台湾等。伴随着旅游业和贸易业的发展,我国其他非疫区出现了输入性病例。类鼻疽病的感染途径主要为经伤口、粘膜、呼吸道、消化道等,其病变可涉及机体所有器官,易造成较高的误诊率和病死率。然而我国目前类鼻疽病的流行病筛查技术存在一定的局限性,在防控方面未实行有效的疾病监测和疾病报告制度,对基层医师和民众疾病知识普及的力度不够。因此,本文旨在提高我国医务工作者对类鼻疽病的重视程度,从类鼻疽病的病原学特征、流行病学特征、临床特征、诊断与治疗、防控措施这五个方面进行详细综述。     

227例类鼻疽病例的流行病学特征

目的 分析海口市海南医学院三家附属医院2000—2019年收治的227例类鼻疽患者的流行病学特征,为类鼻疽的防治、诊断提供理论依据。方法 对227例类鼻疽患者开展回顾性调查,分析其性别、年龄、民族、职业、地区、时间等流行病学特征,并对研究对象进行电话随访。结果 227例类鼻疽患者中,男性202人,占88.5%,女性26人,占11.5%; 40~<60岁年龄段的患者最多,127人,占55.9%;汉族202人,占89.0%,黎族23人,占10.1%;农民为主要患病群体,共91人,占40.1%;患者以东方市分布最多, 42人,占18.5%,海口市次之,41人,占18.1%。类鼻疽病发病时间集中于夏秋季,且9、10月为发病高峰,2016年患病人数最多,34人,占15.0%。最为常见的收治科室为传染科 58 人,占25.6%,其次为呼吸内科46人,占20.3%,外科30人,占13.2%。共随访了62例,随访结果显示,85.5%（53例）的患者痊愈,4.8%（3例）出现复发,9.7%（6例）死亡。结论 中老年、接触疫水和土壤的人群、沿海地区、夏秋季为类鼻疽的高危因素,应加强人们对类鼻疽的认识,做好相应的防治工作。     

Treatment and prophylaxis of melioidosis

Melioidosis, infection with Burkholderia pseudomallei, is being recognised with increasing frequency and is probably more common than currently appreciated. Treatment recommendations are based on a series of clinical trials conducted in Thailand over the past 25 years. Treatment is usually divided into two phases: in the first, or acute phase, parenteral drugs are given for ≥10 days with the aim of preventing death from overwhelming sepsis; in the second, or eradication phase, oral drugs are given, usually to complete a total of 20 weeks, with the aim of preventing relapse. Specific treatment for individual patients needs to be tailored according to clinical manifestations and response, and there remain many unanswered questions. Some patients with very mild infections can probably be cured by oral agents alone. Ceftazidime is the mainstay of acute-phase treatment, with carbapenems reserved for severe infections or treatment failures and amoxicillin/clavulanic acid (co-amoxiclav) as second-line therapy. Trimethoprim/sulfamethoxazole (co-trimoxazole) is preferred for the eradication phase, with the alternative of co-amoxiclav. In addition, the best available supportive care is needed, along with drainage of abscesses whenever possible. Treatment for melioidosis is unaffordable for many in endemic areas of the developing world, but the relative costs have reduced over the past decade. Unfortunately there is no likelihood of any new or cheaper options becoming available in the immediate future. Recommendations for prophylaxis following exposure to B. pseudomallei have been made, but the evidence suggests that they would probably only delay rather than prevent the development of infection.     

Melioidosis in a returned traveller

Melioidosis is an infection endemic to Southeast Asia and Northern Australia, and is associated with significant morbidity and mortality. The present report describes a case of chronic melioidosis in a returning traveller from the Philippines. Clinical suspicion of this illness is warranted in individuals with a history of travel to endemic regions. Safety in handling clinical specimens is paramount because laboratory transmission has been described.     

Characterization of cellular immune response and innate immune signaling in human and nonhuman primate primary mononuclear cells exposed to Burkholderia mallei

Burkholderia pseudomallei infection causes melioidosis and is often characterized by severe sepsis. Although rare in humans, Burkholderia mallei has caused infections in laboratory workers, and the early innate cellular response to B. mallei in human and nonhuman primates has not been characterized. In this study, we examined the primary cellular immune response to B. mallei in PBMC cultures of non-human primates (NHPs), Chlorocebus aethiops (African Green Monkeys), Macaca fascicularis (Cynomolgus macaque), and Macaca mulatta (Rhesus macaque) and humans. Our results demonstrated that B. mallei elicited strong primary pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1β, and IL-6) equivalent to the levels of B. pseudomallei in primary PBMC cultures of NHPs and humans. When we examined IL-1β and other cytokine responses by comparison to Escherichia coli LPS, African Green Monkeys appears to be most responsive to B. mallei than Cynomolgus or Rhesus. Characterization of the immune signaling mechanism for cellular response was conducted by using a ligand induced cell-based reporter assay, and our results demonstrated that MyD88 mediated signaling contributed to the B. mallei and B. pseudomallei induced pro-inflammatory responses. Notably, the induced reporter activity with B. mallei, B. pseudomallei, or purified LPS from these pathogens was inhibited and cytokine production was attenuated by a MyD88 inhibitor. Together, these results show that in the scenario of severe hyper-inflammatory responses to B. mallei infection, MyD88 targeted therapeutic intervention may be a successful strategy for therapy.     

类鼻疽伯克霍尔德菌感染的临床特点与耐药性分析

目的了解我院类鼻疽病的临床特征,探讨早期诊断治疗及该菌的耐药性分析;统计近6年类鼻疽病病死率,并且了解实验室对该菌的细菌学鉴定和药敏试验方法。方法采用回顾性2003年4月~2010年4月期间收治的43例类鼻疽病感染者的临床症状以及治疗、愈后及半年后进行电话随访统计;结果患者起病时多以带有基础疾病时起病或是农作时外伤引起,临床症状多以畏寒、高热、肺部感染、败血症以及脏器损害和细菌毒素引起的全身反应为主要表现,病情较为严重,药敏结果类鼻疽伯霍尔德杆菌对亚胺培南敏感率达100%,对美洛培南、头孢哌酮/舒巴坦、哌拉西林/他唑巴坦敏感率达80%以上,对头孢他啶敏感率为66.7%,而对广谱青霉素类、氨基糖苷类耐药,对头孢类有不同程度的耐药。结论该病临床特征多样,首诊困难,误诊率高,广谱抗生素治疗无效,易延误病情,住院时间长,治疗成本高,应提高临床医生对此病的认识和警惕以尽快确诊。目前认为碳青霉烯类为首选抗生素,临床用药应为以碳青霉烯类为主的两种抗生素以上联合用药效果好。     

Multiple hepatic and splenic abscesses due to Burkholderia pseudomallei

We report a case of melioidosis in an alcoholic and diabetic male patient presenting with multiple hepatic and splenic abscesses. Melioidosis is caused by an environmental bacterium Burkholderia pseudomallei. The clinical manifestations vary from asymptomatic infection to fulminant septic shock with abscesses in multiple internal organs. The treatment is prolonged with parenteral antibiotics in intensive phase followed by oral antibiotics in eradication phase till disease resolution. Due to varied clinical presentations, high index of suspicion coupled with adequate laboratory support is essential for rapid diagnosis and prompt initiation of optimal antibiotic therapy.     

海南岛感染性疾病类鼻疽血清学调查

目的 了解海南岛各类感染性疾病假鼻疽伯克霍尔德菌的感染状况。方法 采用IHA法对517例患有感染性疾病患检测其类鼻疽抗体。结果 517例患有感染性疾病的患检出类鼻疽抗体阳性145例，阳性率最高达28．0％，其中组织器官脓肿患检出类鼻疽抗体阳性率最高达36．2％；依次为溃疡感染33．3％；心肌炎33．3％；阑尾炎31．4％；腹膜炎30．8％；前列腺炎30．0％；肺部感染27．5％；胰腺炎22．2％；结核病21．4％；关节炎21．1％；肾炎16．6％；糖尿病并感染25．0％；其它感染29．2％。结论 海南岛假鼻疽伯克霍尔德菌在感染性疾病中伴有感染甚为普遍，甚至是部分感染性疾病的病因，必须引起疫区临床医生的重视。     

CD4+ T-cell immunity to the Burkholderia pseudomallei ABC transporter LolC in melioidosis

Burkholderia pseudomallei causes melioidosis, a disease with a wide range of possible outcomes, from seroconversion and dormancy to sepsis and death. This spectrum of host-pathogen interactions poses challenging questions about the heterogeneity in immunity to B. pseudomallei. Models show protection to be dependent on CD4(+) cells and IFN-γ, but little is known about specific target antigens. Having previously implicated the ABC transporter, LolC, in protective immunity, we here use epitope prediction, HLA-binding studies, HLA-transgenic models and studies of T cells from seropositive individuals to characterize HLA-restricted LolC responses. Immunized mice showed long-lasting memory to the protein, whereas predictive algorithms identified epitopes within LolC that subsequently demonstrated strong HLA class II binding. Immunization of HLA-DR transgenics with LolC stimulated T-cell responses to four of these epitopes. Furthermore, the responsiveness of HLA transgenics to LolC revealed a hierarchy supportive of HLA polymorphism-determined differential susceptibility. Seropositive human donors of diverse HLA class II types showed T-cell responses to LolC epitopes, which are conserved among Burkholderia species including Burkholderia cenocepacia, associated with life-threatening cepacia complex in cystic fibrosis patients and Burkholderia mallei, which causes glanders. These findings suggest a role for LolC epitopes in multiepitope vaccine design for melioidosis and related diseases.