Protists as opportunistic pathogens: public health impact in the 1990s and beyond

Protist organisms (protozoa and fungi) have become increasingly prominent as opportunistic pathogens among persons infected with human immunodeficiency virus (HIV) and among organ transplant recipients--two immunocompromised populations that have increased dramatically in the past two decades. Pneumocystis carinii pneumonia continues to be the most common serious opportunistic infection (OI) among HIV-infected persons in the United States, occurring frequently among persons not previously receiving medical care. Toxoplasmosis, cryptococcosis, cryptosporidiosis, and isosporiasis occur frequently in HIV-infected persons in the developing world. Candidiasis and aspergillosis are common OIs in organ transplant recipients. As these populations of immunosuppressed patients continue to expand worldwide new OIs caused by protist pathogens are likely to emerge.     

艾滋病合并真菌感染研究概述

真菌感染是艾滋病患者最常见、比重最大的机会性感染,是最重要致死原因之一。常见的机会性真菌感染包括：念珠菌病、卡氏肺孢子菌病、隐球菌病、马尔尼菲蓝状菌感染、组织胞浆菌病、球孢子菌病。本文介绍了机体的CD4⁺T淋巴细胞与机会性真菌感染关系以及常见的真菌感染的流行病学、发病机制、临床表现、诊断、治疗、预防等方面研究进展。提高临床医生对这类真菌感染系统全面的认识,有助于做到早期诊断、早期治疗,合理选择抗真菌药物,从而提高患者生存质量,延长生存时间。     

Cryptococcosis as an opportunistic infection in immunodeficiency secondary to paracoccidioidomycosis

We describe the case reports of two patients with immunodeficiency secondary to paracoccidioidomycosis (PCM) and opportunistic Cryptococcus neoformans infections. Secondary immunodeficiency likely occurred as a consequence of the intestinal loss of proteins and lymphocytes associated with malabsorption syndrome due to obstructed lymphatic drainage. Both patients had had severe abdominal involvement during the acute PCM disease. Immunological evaluation showed cellular and humoral immunity impairment. Cryptococcosis manifested as relatively well circumscribed lesions: osteolytic lesions of the skull in one patient, and pulmonary nodules in the other. The latter was treated surgically and with amphotericin B, whereas the other was treated with the combination amphotericin-B and flucytosine. Both patients had a good response to treatment with complete regression of the lesions. They have now 2 and 4 years of follow-up with maintenance therapy and no indication of reactivation of the infection. PCM also did not reactivate. The clinical and immunological characteristics of these patients are discussed and compared to the opportunistic C. neoformans infections of AIDS and transplant patients.     

Pathogen evolution within host individuals as a primary cause of senescence

This paper discusses a novel theory of senescence: the community of pathogens within each host individual evolves during the life-time of the host, and in doing so progressively reduces host vigour. I marshal evidence that asymptomatic host individuals maintain persistent populations of viral pathogens; that these pathogens replicate; that they are often extremely variable; that selection within hosts causes the evolution of pathogens better able to exploit the host; that selection is host-specific; and that such evolving infections cause appreciable and progressive deterioration. Experimental approaches to testing the theory are discussed.     

"Mixing" as an ethnoetiology of HIV/AIDS in Malaysia's multinational factories

Minah Karan, the stigmatizing label appended to Malay factory women in the 1980s, signaled a dangerous female sexuality that risked spreading beyond the factory gates and infecting Malaysia's idea(l)s of its traditional kampung culture. This article narrates how Minah Karan, as the former antihero of development, was reconstituted in the 1990s, with the government's labeling of factories as "high-risk settings" for HIV/AIDS. This is an ethnoetiology based not on any evidential epidemiological data but on the racial and gendered "mixing" that transpires behind factory walls: a fear that the "mixing of the sexes" means ipso facto "sexual mixing" among the races. The article demonstrates how importation of the high-risk label articulates at the local level the new and contested linkages, economic, religious, and scientific, constitutive of globalization. The pragmatic nature and imperatives of this high-risk process are discerned in factory women's accounts of how they negotiate the interactional imperatives of factory work, because transnational structures of productivity violate the social boundaries that have long connoted political stability, moral integrity, ethnic community, and individual safety. The article concludes by questioning whether ethnoetiologies, especially when they concern sexual networks, become social etiologies, because this would locate ethnoetiologies as central to conventional public health praxis rather than as ethnographic exotica in the margins.     

Peptide nucleic acids as epigenetic inhibitors of HIV-1

Summary The advent of highly active antiretroviral therapy (HAART) was once perceived to have transformed deadly HIV/AIDS into a treatable, chronic infectious disease. However, mounting evidence now suggests that the prevalence of multi-drug resistant HIV (MDR-HIV) infection is steadily rising among newly infected individuals in the HAART-experienced countries, raising a concern for a future outbreak of MDR-HIV/AIDS. Our global fight against AIDS must include sustained effort to search and discover a new therapeutic modality for HIV infection. Of plausible viral targets explored to date, HIV gene-targeting approach has not yet seen a considerable success in vivo. The pursuit of anti-HIV gene intervention should include the identification of critical gene targets as well as the optimization of biomolecules that can effectively interact with the intended targets. Using unmodified peptide nucleic acids (PNA) as a biomolecular tool, we discovered a potentially critical HIV gene segment within gag-pol encoding gene. Antisense PNA targeting this specific region effectively disrupted a translation of HIV gag-pol mRNA, abolishing the virion production from chronically HIV-infected cells. This exemplifies the possibility that epigenic HIV inhibitors may be developed in the coming years, if emerging novel technologies permit sufficient and stable in vivo delivery of PNA or other similarly effective biomolecules.     

Peptide nucleic acids as epigenetic inhibitors of HIV-1

The advent of highly active antiretroviral therapy (HAART) was once perceived to havetransformed deadly HIV/AIDS into a treatable, chronic infectious disease. However, mountingevidence now suggests that the prevalence of multi-drug resistant HIV (MDR-HIV) infection issteadily rising among newly infected individuals in the HAART-experienced countries, raising aconcern for a future outbreak of MDR-HIV/AIDS. Our global fight against AIDS must include sustainedeffort to search and discover a new therapeutic modality for HIV infection. Of plausible viraltargets explored to date, HIV gene-targeting approach has not yet seen a considerable success invivo. The pursuit of anti-HIV gene intervention should include the identification of critical genetargets as well as the optimization of biomolecules that can effectively interact with theintended targets. Using unmodified peptide nucleic acids (PNA) as a biomolecular tool, we discovereda potentially critical HIV gene segment within gag-polencoding gene. Antisense PNA targetingthis specific region effectively disrupted a translation of HIV gag-polmRNA, abolishing thevirion production from chronically HIV-infected cells. This exemplifies the possibility that epigenic HIV inhibitors may be developed in the coming years, if emerging novel technologies permitsufficient and stable in vivo delivery of PNA or other similarly effective biomolecules.     

Peptide nucleic acids as epigenetic inhibitors of HIV-1

Summary The advent of highly active antiretroviral therapy (HAART) was once perceived to have transformed deadly HIV/AIDS into a treatable, chronic infectious disease. However, mounting evidence now suggests that the prevalence of multi-drug resistant HIV (MDR-HIV) infection is steadily rising among newly infected individuals in the HAART-experienced countries, raising a concern for a future outbreak of MDR-HIV/AIDS. Our global fight against AIDS must include sustained effort to search and discover a new therapeutic modality for HIV infection. Of plausible viral targets explored to date, HIV gene-targeting approach has not yet seen a considerable success in vivo. The pursuit of anti-HIV gene intervention should include the identification of critical gene targets as well as the optimization of biomolecules that can effectively interact with the intended targets. Using unmodified peptide nucleic acids (PNA) as a biomolecular tool, we discovered a potentially critical HIV gene segment within gag-pol encoding gene. Antisense PNA targeting this specific region effectively disrupted a translation of HIV gag-pol mRNA, abolishing the virion production from chronically HIV-infected cells. This exemplifies the possibility that epigenic HIV inhibitors may be developed in the coming years, if emerging novel technologies permit sufficient and stable in vivo delivery of PNA or other similarly effective biomolecules.     

Accounting for data errors discovered from an audit in multiple linear regression

A data coordinating team performed onsite audits and discovered discrepancies between the data sent to the coordinating center and that recorded at sites. We present statistical methods for incorporating audit results into analyses. This can be thought of as a measurement error problem, where the distribution of errors is a mixture with a point mass at 0. If the error rate is nonzero, then even if the mean of the discrepancy between the reported and correct values of a predictor is 0, naive estimates of the association between two continuous variables will be biased. We consider scenarios where there are (1) errors in the predictor, (2) errors in the outcome, and (3) possibly correlated errors in the predictor and outcome. We show how to incorporate the error rate and magnitude, estimated from a random subset (the audited records), to compute unbiased estimates of association and proper confidence intervals. We then extend these results to multiple linear regression where multiple covariates may be incorrect in the database and the rate and magnitude of the errors may depend on study site. We study the finite sample properties of our estimators using simulations, discuss some practical considerations, and illustrate our methods with data from 2815 HIV-infected patients in Latin America, of whom 234 had their data audited using a sequential auditing plan.     

The role of the local microbial ecosystem in respiratory health and disease

Respiratory tract infections are a major global health concern, accounting for high morbidity and mortality, especially in young children and elderly individuals. Traditionally, highly common bacterial respiratory tract infections, including otitis media and pneumonia, were thought to be caused by a limited number of pathogens including Streptococcus pneumoniae and Haemophilus influenzae. However, these pathogens are also frequently observed commensal residents of the upper respiratory tract (URT) and form—together with harmless commensal bacteria, viruses and fungi—intricate ecological networks, collectively known as the ‘microbiome’. Analogous to the gut microbiome, the respiratory microbiome at equilibrium is thought to be beneficial to the host by priming the immune system and providing colonization resistance, while an imbalanced ecosystem might predispose to bacterial overgrowth and development of respiratory infections. We postulate that specific ecological perturbations of the bacterial communities in the URT can occur in response to various lifestyle or environmental effectors, leading to diminished colonization resistance, loss of containment of newly acquired or resident pathogens, preluding bacterial overgrowth, ultimately resulting in local or systemic bacterial infections. Here, we review the current body of literature regarding niche-specific upper respiratory microbiota profiles within human hosts and the changes occurring within these profiles that are associated with respiratory infections.     

On the uniqueness of endemic equilibria of an HIV/AIDS transmission model for a heterogeneous population

In this paper, we examine an HIV/AIDS transmission model which has been widely used for studying the spread of HIV/AIDS through sexual contact. Some sufficient conditions are obtained for the uniqueness of endemic equilibrium. We also present a two-group model whose no-disease equilibrium is unstable but it has at least three positive endemic equilibria.     

颅脑损伤患者下呼吸道感染病原菌分布及耐药性分析

目的 探讨桐乡市第一人民医院颅脑损伤患者下呼吸道感染病原菌的分布及耐药性,帮助临床合理使用抗菌药物.方法 采用VITEK-2细菌鉴定及药敏分析系统,对113例颅脑损伤患者下呼吸道感染痰标本分离出的病原菌进行鉴定和耐药性分析.结果 113例患者中共分离出病原菌179株,其革兰阴性杆菌122株,占68.1%,以肺炎克雷伯菌...     

Pinimenthol ointment in patients suffering from upper respiratory tract infections – A post-marketing observational study

In order to gain further experience regarding the tolerability of Pinimenthol^® ointment¹ in adolescents (⩾12 years) and adults suffering from upper respiratory tract infections, a post-marketing observational study was performed. In this study, data of 3060 patients were collected (64.9% prospectively over an individual observation period of 5–14 days, 35.1% retrospectively). The prospective documentation also comprised data concerning treatment effects.Sample size of the post-marketing observational study was calculated in the way that adverse drug reactions with an event probability of at least 1:1000 would occur within the study at least once with a probability of 95%.Most patients suffered from cold, acute or chronic bronchitis, bronchial catarrh or hoarseness. Pinimenthol^® ointment was prescribed to inunction (29.6%), inhalation (17.3%) or inunction and inhalation (53.1%), respectively. The mean duration of study participation was 8.0±3.4 days.The tolerability was rated as excellent or good by 96.7% of physicians and 95.7% of patients. A total of 22 patients (0.7%) reported adverse drug reactions which mostly affected the skin or mucus membrane and therefore correspond to the expected adverse effects profile of Pinimenthol^® ointment. The treatment effect was mostly judged as excellent or good (physicians: 88.3%; patients: 88.1%).In conclusion, the study confirms Pinimenthol^® ointment as a well tolerated therapy option for upper respiratory tract infections in both adolescents and adults.     

HIV/AIDS患者CD4水平对甲状腺功能影响的比较研究

目的观察HIV/AIDS患者甲状腺功能的变化,了解HIV对内分泌的影响。方法检测168例HIV/AIDS患者TT4、TT3、FT4、FT3、TSH,并分析不同CD4水平对甲状腺功能影响。结果HIV/AIDS患者甲状腺功能可保持正常,但低CD4组的FT3、TSH水平低于高CD4组。结论HIV/AIDS患者甲状腺功能可保持正常,但HIV感染不同阶段会对内分泌系统有一定影响。HIV感染对甲状腺影响的具体机制尚不十分清楚,利用动物模型进行进一步研究非常必要。     

The changing face of pediatric respiratory tract infections: how human metapneumovirus and human bocavirus fit into the overall etiology of respiratory tract infections in young children

Lower respiratory tract infections are one of the leading causes of morbidity and mortality in children worldwide. Recent technological advances in the field of molecular biology have allowed virologists to detect many previously undetected viral pathogens. Two of these, human metapneumovirus (hMPV) and human bocavirus (HBoV), are of particular clinical interest to pediatric health care providers. This review discusses the most common viral respiratory infections in children, explores the role of newly discovered respiratory pathogens, and describes techniques for the diagnosis of viral respiratory infections.