Influenza

For three decades, virologists and public health authorities have warned that influenza virus A will soon cause a new dangerous pandemic. The spread of avian influenza virus A/H5N1 has been under close observation since 1997 because of sporadic lethal transmission to humans [1–3]. Ultimately, no more than approximately 600 cases were reported, with no subclinical spread in the human population despite a worldwide avian epidemic [4]. This is just the opposite of other wide-spread infections, e.g. enteroviruses, as recently disclosed by a seroepidemiological study on hand-foot-mouth disease [5]. With regard to human-adapted influenza virus A subtypes, an increasing number of drug-resistant strains have been isolated, undermining the concept of a possible common chemoprophylaxis [1, 2]. When swine-origin influenza virus A/H1N1v emerged in Mexico in 2009 and spread throughout the world, a new influenza pandemic was declared by the WHO despite the fact that, from the start, the disease appeared to take a more benign course than seasonal flu [6, 7]. In the next 2 years, no dramatic mutations of the virus genome and, in particular, no new virulence factor was detected. Current knowledge on influenza A viral PB1-F2 has been reviewed [8]. Whether differences in the activation of signal cascades in infected cells as opposed to other influenza A viruses bear biological relevance remains to be determined [9]. Adjuvanted and non-adjuvanted vaccines were developed and shown to be effective. However, severe cases of H1N1v infections were fortunately relatively infrequent. Thus, the indication for vaccination remained debatable, and compliance of the vaccination offered by public health authorities was poor. From the beginning, it was pointed out that adverse effects of vaccination with adjuvanted vaccines could not be excluded for want of clinical trials [10]. Remarkable cases of narcolepsy have recently been reported in Sweden, Finland, and China, where large parts of the population have been vaccinated. Officially, however, there is no formal proof for an etiological connection between vaccination and any severe side effects [11]. Thereby, the question whether sufficient vigilance in observation has been maintained calls for critical assessment. The vaccination policy has been subject to discussion [12]. Pandemrix, a frequently used vaccine against H1N1v, has also proven to be efficacious in immunocompromised patients after an additional booster [13], as shown by hemagglutination inhibition tests [14].

Seroepidemiological studies revealed that, after the first wave, about one-third of population formed specific antibodies against H1N1v [15], while the seroepidemiology of the conventional influenza viruses remained stable [16, 17]. This indicates that subclinical H1N1v infections are very frequent and further attests to the relatively benign nature of the virus. As an alternative to neuraminidase blockers, which may be impaired by resistance development, new drugs have been investigated with regard to anti-viral and anti-inflammatory efficacy [18–21]. These agents have not yet found their way into the clinic. As a “bystander” result of research on influenza virus A, a virus strain was developed as an oncolytic agent in tumor therapy [22].

Viral hepatitis and AIDS

Treatment of hepatitis C has seen significant improvements in the last years, and new concepts have been established for patients undergoing liver transplantation [23]. Viral hepatitis C is ubiquitously endemic. The majority of HCV infections persist lifelong in coexistence with antibodies that may contribute to immunopathogenesis via formation of immune complexes [24].

Diagnostic and therapeutic strategies to combat HIV, HBV, and HCV have been reviewed [25]. The analysis of CTL responses to Gag and Nef gene products released during HIV infection is in progress [26]. The frequency of HBV and HCV coinfections in AIDS patients has been reevaluated [27], and the concept that patients undergoing successful therapy suffer less frequently from opportunistic infections and tumors has been corroborated.

These and related studies profit from the ongoing development of molecular diagnostic tools that allow the spread of HIV infection to be rapidly and reliably traced [28].

CMV and other herpesviruses

CMV infection is opportunistically reactivated in immunocompromised patients; reciprocally, CMV infection in turn compromises the immune system. CMV was once considered a relevant etiological agent triggering atherosclerosis. However, several lines of reasoning convened to challenge this concept [29], and recent epidemiologic data indeed do not support the hypothesis. The prevalence of CMV infection decreases in population with high socioeconomic status [30], while the incidence of atherosclerosis increases. An independent issue relates to the possibility of oncomodulation by CMV, and the evidence that CMV infection may enhance the growth of glioma and other CNS tumors has been reviewed [31]. The possibility that application of anti-virals (ganciclovir) may impair the tumor progress warrants further investigation [32]. Such studies will be aided by the availability of sensitive and specific molecular methods for CMV detection [33, 34], for evaluation of therapy resistance [35] and for assessment of cellular immune responses [36]. Similar molecular methods are also applied to HSV and VZV infections to analyze viral resistance to therapy [37, 38] and to pursue molecular epidemiological studies [39, 40]. A monoclonal protective antibody against HSV was developed as an alternative to chemotherapy [41]. In this context, a review has addressed the topic of single-domain antibodies as promising new agents for immunotherapy [42].

Pathogen variation and host response in infectious diseases

Measles is a classic immunocompromising infectious disease with CD 28 and IL 4 playing central roles in controlling the balance between immunity and inflammation [43]. Mechanisms underlying pathogenicity of the virus have been reviewed [44] with particular reference to the problem of virus-induced CNS disease [45]. Molecular pathways to pathogen variation and adaptation to the host have been reviewed for E. coli [46] (16), Bordetella [47], and Neisseria [48, 49]. Of related interest are the regulation of white-opaque switch in Candida albicans [50] and the role of evolutionary conserved signaling systems in Echinococcus with regard to host-parasite interaction [51].

The interplay between virus-induced immune suppression and tuberculosis continues to represent a recurring theme [52]. Papers have been devoted to improvement of laboratory diagnoses of Mycobacterium infections [53], on vaccination-relevant studies regarding immunocellular reactions to M. tuberculosis [54], as well as to current concepts on the development of a vaccine [55, 56]. Of distinct interest, related work has led to progress on vaccine development against buruli ulcer disease [57]. New strategies for antibacterial prophylaxis and vaccination based on the use of bacteriophages [58], of microparticle- or nanoemulsion-based vaccines [59, 60], or by stimulation of innate immunity [61] have been presented.

Papers have dealt with the adaptation of brucella to their intracellular niche [62], and with the virulence determinants involved in this process [48]. A novel link between bacterial invasion and host response was uncovered in a study that showed autophagia to be induced in cells attacked by membrane-damaging bacterial toxins [63]. This paper was selected by the Faculty of 1,000 as one of the most important publications in 2010. Another theme that is currently of wide interest pertains to the phenomenon of neutrophil extracellular traps (NETs). Current knowledge, particularly in regard to the possible pathophysiological roles of NETs in immune disorders, was the subject of a review [64].

Since the first report on the possible presence of C. pneumoniae in brains of patients with Alzheimer disease [65], chronic chlamydial infections have been discussed as a possible cause of this widespread affliction. While there is no doubt that Chlamydia pneumoniae can infect mononuclear cells [66], a critical review has underlined the fact that the link between chlamydial infection and Alzheimer disease is still speculative and further work is called for [67]. Of note, suggestive evidence for a causative role of spirochetal infections in Alzheimer’s disease has also emerged in recent years [68].

Tropical infectious diseases and emerging infections in Europe

Globalization and climatic change are causing an ever increasing number of exotic infections in Europe. Reports in this journal have dealt with Hantavirus infections in Germany [69, 70], travel-associated Ross River and Dengue virus infections [71, 72] as well as with the epidemiology of Chikungunya virus infection [73]. A review has dealt with lessons learned from Leishmaniasis regarding the determinants of success or failure of intracellular cutaneous parasites [74].

To sum, papers recently published in this journal have addressed important themes in medical microbiology and immunology. An increasing impact factor attests to the successful efforts of the journal to serve the scientific community by publishing timely and insightful articles on themes of high relevance and widespread interest.