结核病疫情及对策

为评估全球结核病（tuberculosis, TB）疫情及防治工作进展,WHO自1997年开始,每年出版一期全球结核病控制年报。为了解全国TB疫情,评价防治工作进展,为制订TB防治规划提供依据,我国于1979年、1984-1985年、1990年、2000年和2010年先后开展了5次全国结核病流行病学抽样调查。笔者对全球及中国TB疫情及防治策略进行了归纳总结,供各级疾病预防控制机构（结核病防治机构）参考,以统一、规范TB疫情资料的使用。     

Tuberculosis presenting as inflammatory bowel disease

Two cases are reported of idiopathic inflammatory total colitis in patients with a previous history of tuberculosis. One showed colonoscopic and radiologic features of Crohn's disease and the other was diagnosed as ulcerative colitis. Tuberculous organisms were identified in the mesenteric nodes in one patient, but were not detected in the other. Both patients improved with antituberculous treatment. This report emphasizes the importance of considering tuberculosis in patients presenting with idiopathic inflammatory bowel disease of the colon and raises speculation on the possible infective etiology of Crohn's disease.     

Tuberculosis epidemic in a technical center

A tuberculosis epidemic occurred in a class at a technical center in a large furniture company. An index case was a male student who had a severe family history of tuberculosis and his sputum smear was Guffky 3. PPD skin test and routine chest X-ray examination were immediately done on the forty-two classmates. As the result of these examinations, the distribution of maximum diameter of erythema in PPD skin test showed bimodal distribution, and tuberculosis was discovered in five patients by chest X-ray examination. During follow up for eighteen months another three new patients were found. In this company, routine chest X-ray examination had been carried out. The patient's delay and insufficient ventilation in the dormitory were considered to be the main causes of the tuberculosis epidemic.     

From the Cover: Optimizing infectious disease interventions during an emerging epidemic

The emergence and global impact of the novel influenza A(H1N1)v highlights the continuous threat to public health posed by a steady stream of new and unexpected infectious disease outbreaks in animals and humans. Once an emerging epidemic is detected, public health authorities will attempt to mitigate the epidemic by, among other measures, reducing further spread as much as possible. Scarce and/or costly control measures such as vaccines, anti-infective drugs, and social distancing must be allocated while epidemiological characteristics of the disease remain uncertain. Here we present first principles for allocating scarce resources with limited data. We show that under a broad class of assumptions, the simple rule of targeting intervention measures at the group with the highest risk of infection per individual will achieve the largest reduction in the transmission potential of a novel infection. For vaccination of susceptible persons, the appropriate risk measure is force of infection; for social distancing, the appropriate risk measure is incidence of infection. Unlike existing methods that rely on detailed knowledge of group-specific transmission rates, the method described here can be implemented using only data that are readily available during an epidemic, and allows ready adaptation as the epidemic progresses. The need to observe risk of infection helps to focus the ongoing planning and design of new infectious disease surveillance programs; from the presented first principles for allocating scarce resources, we can adjust the prioritization of groups for intervention when new observations on an emerging epidemic become available.     

Pediatric malignancies presenting as a possible infectious disease

Background  

The clinical, laboratory, and radiological features of malignancy can overlap with those of infection. The purpose of this study was to determine the findings in children who were initially thought to have an infectious disease but ultimately proved to have a malignancy.     

Tuberculosis of the liver presenting as peripheral vascular disease

Peripheral vascular disease in African males may be associated with a tuberculous infection elsewhere in the body. The case history is described of a patient who presented with gangrenous lesions of both feet and was found to have tuberculosis of the liver. The lesions on the feet healed within 2 months of starting anti-tuberculosis chemotherapy.     

Spherical nucleic acids as an infectious disease vaccine platform

Despite recent efforts demonstrating that organization and presentation of vaccine components are just as important as composition in dictating vaccine efficacy, antiviral vaccines have long focused solely on the identification of the immunological target. Herein, we describe a study aimed at exploring how vaccine component presentation in the context of spherical nucleic acids (SNAs) can be used to elicit and maximize an antiviral response. Using COVID-19 as a topical example of an infectious disease with an urgent need for rapid vaccine development, we designed an antiviral SNA vaccine, encapsulating the receptor-binding domain (RBD) subunit into a liposome and decorating the core with a dense shell of CpG motif toll-like receptor 9 agonist oligonucleotides. This vaccine induces memory B cell formation in human cells, and in vivo administration into mice generates robust binding and neutralizing antibody titers. Moreover, the SNA vaccine outperforms multiple simple mixtures incorporating clinically employed adjuvants. Through modular changes to SNA structure, we uncover key relationships and proteomic insights between adjuvant and antigen ratios, concepts potentially translatable across vaccine platforms and disease models. Importantly, when humanized ACE2 transgenic mice were challenged in vivo against a lethal live virus, only mice that received the SNA vaccine had a 100% survival rate and lungs that were clear of virus by plaque analysis. This work underscores the potential for SNAs to be implemented as an easily adaptable and generalizable platform to fight infectious disease and demonstrates the importance of structure and presentation in the design of next-generation antiviral vaccines.

Infectious diseases have long threatened humanity due to their ability to rapidly spread and mutate across populations, infecting many people (1). The rapid and global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, emphatically revealed this and highlighted the importance of effective vaccination strategies to mitigate the spread and infectivity of viruses. Vaccination strategies are increasingly important as we consider the potential for emerging infectious diseases still to come (2, 3). The ability to rapidly adapt vaccine platforms through advancement of previous knowledge can be a huge asset. In particular, protein-based subunit vaccines can reduce vaccine production costs, while diminishing vaccine side effects. However, ultimate outcomes of protein-based subunit vaccine performance are difficult to correlate between candidates (4).An example of this is the influenza vaccine, which has relied on various simple mixtures of antigenic protein subunit target and adjuvant in solution to induce immune responses (5). As a result, influenza vaccine effectiveness has varied dramatically by year, with a low of 10% effectiveness in 2004–2005 and a high of 60% effectiveness in 2010–2011 (6, 7). This high variability is often attributed to the level of antigenic match between circulating viruses and vaccine strains. However, recent work has shown that the same antigen target can be more or less antigenic depending on the mode of presentation and delivery to the immune system (7, 8). By harnessing this concept, which we have termed rational vaccinology (9), we can greatly aid efforts to correlate vaccine design with performance by providing structurally informed and optimized vaccine platforms that can be readily and quickly adapted to new disease targets.Rational vaccinology has been implemented successfully for vaccines against cancer, where nanoscale changes have dramatically altered immune activation and tumor reduction (9–11). The application of this approach toward infectious disease has yet to be fully realized, and the potential for it to dramatically impact the success of vaccine development remains untapped. Herein, we have implemented spherical nucleic acid (SNA) nanotechnology as a tool to explore the impact of vaccine presentation when applied to infectious disease, using COVID-19 as a case study. SNAs comprise a nanoparticle core surrounded by a dense radial arrangement of oligonucleotides (12–14). Like many nanovaccine platforms, the SNA is biocompatible and comprises naturally found molecules in cellular biology. Importantly, however, the SNA provides key advantages over other nanovaccine platforms. Specifically, the SNA platform is highly modular, enabling the elucidation of important structure–function relationships. Moreover, the SNA is effective at entering cells rapidly and in high quantities through scavenger receptor A–mediated endocytosis and is resistant to nuclease degradation, due to the dense arrangement of oligonucleotides (15, 16). Moreover, by using a DNA shell containing immunostimulatory CpG motif DNA, SNAs robustly activate the innate immune system through toll-like receptor 9 (TLR9) (9, 17) and exhibit efficient lymph node drainage and high codelivery of adjuvant and antigen to antigen-presenting cells (9, 11). These properties have been harnessed in this work to maximize humoral responses and generate antibodies that are effective at neutralization in pseudoviral assays, capable of withstanding mutations to still bind the target, and protective in mice against a lethal viral challenge. Overall, we report enhancement in immune responses, leading to a 100% survival rate in a lethal viral challenge, which can be achieved through utilization of the SNA’s privileged architecture.     

Tuberculosis a re-emerging disease

Two billion people, nearly one-third of the population worldwide, are infected by M. tuberculosis. Since 2008, the number of foreign TB cases in Italy has overtaken native cases. Even though TB prevalently affects elderly Italian natives, the diagnosis of the disease in these subjects is difficult and frequently delayed because of the low index of suspicion due to loss of clinical experience. Moreover, the large use of TNF inhibitors has created a new risk group for the disease, highlighting the need for tougher screening practices to reduce new cases of severe TB. Immigration from high-incidence countries like Romania has increased the number of cases of multi-drug resistant TB. These cases are usually difficult to treat because of fewer treatment options and also difficulty in managing patients with adverse socioeconomic conditions such as homelessness. It is mandatory that young doctors acquire experience in the diagnosis and treatment of TB, a disease that is not so infrequent as it was a decade or two ago.     

2009年全球传染病疫情聚焦

2009年全球各种传染病频繁暴发和流行,3月份至年底各大洲均面临甲型H1N1流感的严峻挑战,防控形势非常严峻。现就2009年全球传染病重点疫情、疫点,结合我国防控情况作一回顾。