Critical Roles of Complement and Antibodies in Host Defense Mechanisms against Neisseria meningitidis as Revealed by Human Complement Genetic Deficiencies

Certain complement defects are associated with an increased propensity to contract Neisseria meningitidis infections. We performed detailed analyses of complement-mediated defense mechanisms against N. meningitidis 44/76 with whole blood and serum from two adult patients who were completely C2 or C5 deficient. The C5-deficient patient and the matched control were also deficient in mannose-binding lectin (MBL). The proliferation of meningococci incubated in freshly drawn whole blood was estimated by CFU and quantitative DNA real-time PCR. The serum bactericidal activity and opsonophagocytic activity by granulocytes were investigated, including heat-inactivated postvaccination sera, to examine the influence of antimeningococcal antibodies. The meningococci proliferated equally in C2- and C5-deficient blood, with a 2 log₁₀ increase of CFU and 4- to 5-log₁₀ increase in DNA copies. Proliferation was modestly decreased in reconstituted C2-deficient and control blood. After reconstitution of C5-deficient blood, all meningococci were killed, which is consistent with high antibody titers being present. The opsonophagocytic activity was strictly C2 dependent, appeared with normal serum, and increased with postvaccination serum. Serum bactericidal activity was strictly dependent on C2, C5, and high antibody titers. MBL did not influence any of the parameters observed. Complement-mediated defense against meningococci was thus dependent on the classical pathway. Some opsonophagocytic activity occurred despite low levels of antimeningococcal antibodies but was more efficient with immune sera. Serum bactericidal activity was dependent on C2, C5, and immune sera. MBL did not influence any of the parameters observed.Systemic meningococcal disease evolves when pathogenic Neisseria meningitidis breach the pharyngeal mucosa and start proliferating in the circulation (36, 44). The majority of the patients develops low-grade bacteremia leading to meningitis with a comparatively low case-fatality rate if adequate antibiotic treatment is given early (44). A minority develops fulminant sepsis caused by massive bacterial proliferation in the circulation, resulting in a very high case-fatality rate (44). A number of genetic disorders and polymorphisms in the host that influence the clinical presentation and outcome have been implicated in the response to intruding meningococci (4, 9).The complement system plays a crucial part in the host defense against systemic meningococcal disease (39). Acquisition of serum bactericidal antibodies correlates with protection (14, 16), whereas other mechanisms, primarily opsonophagocytosis, may also be important (1, 47). Deficiencies of the complement system affecting the alternative pathway, C3, and the terminal pathway have for a long time predominantly been associated with increased susceptibility to meningococcal disease (12, 13). Also, the rather common deficiency of mannose-binding lectin (MBL) has been associated with meningococcal disease, but only in early childhood (8, 11, 15, 19, 45). C2 deficiency, which apart from MBL deficiency is the most common inherited complement deficiency affecting about 1/20,000 of Caucasians (41), appears to be associated with a wide range of infections with encapsulated bacteria of which Streptococcus pneumoniae is the most frequent causative agent, whereas infections due to N. meningitidis occur less frequently (12, 25).In the present study blood samples from two individuals being genetically completely deficient in complement factor 2 (C2) or complement factor 5 (C5) and MBL were used to examine details regarding the specific roles of different parts of the complement system in the protection against serogroup B meningococcal disease. Bacterial survival and proliferation was examined in freshly drawn whole blood. Opsonophagocytic activity (OPA) and serum bactericidal activity (SBA), as well as the role of antimeningococcal antibodies, were studied separately. Functionally active and highly purified complement components were used for reconstitution experiments both of whole blood and of serum in order to confirm the specific roles of these components.     

Modified condylotomy versus conventional conservative treatment in painful reciprocal clicking—a preliminary prospective study in eight patients

Modified condylotomy may be relevant in severe painful reciprocal clicking of the temporomandibular joint (TMJ) where conservative treatment is insufficient. The effect of the modified condylotomy was analyzed and compared with conventional nonsurgical treatment in a randomized pilot study of eight patients, 19–44 years of age, with severe painful reciprocal clicking. Before and after treatment, assessments were performed by subjective reports, clinical recordings, and blinded evaluations of radiography and magnetic resonance imaging (MRI). Based on the clinical evaluations before treatment, all conditions were disc displacements with reduction and arthralgia (Research diagnostic criteria for temporomandibular disorders), but based on MRI, one patient had disc displacement without reduction and another had normal disc position. The treatment effect was significantly better and the disorders were significantly more reduced with condylotomy than with conventional nonsurgical treatment (P < 0.05, Mann–Whitney U test). In the surgical group, the clicking and locking had disappeared, the pain during function was significantly reduced (P < 0.05, Friedman ANOVA), and in two patients the disc position was normalized. The clicking still persisted in the nonsurgical patients and the disc position was unchanged. Our conclusion is that modified condylotomy is a promising option to reduce symptoms and signs in severe painful reciprocal clicking.     

Spatial distribution of Echinococcus multilocularis, Svalbard, Norway

In Svalbard, Norway, the only intermediate host for Echinococcus multilocularis, the sibling vole, has restricted spatial distribution. A survey of feces from the main host, the arctic fox, showed that only the area occupied by the intermediate host is associated with increased risk for human infection.     

Rare Cancers and Social Media: Analysis of Twitter Metrics in the First 2 Years of a Rare-Disease Community for Myeloproliferative Neoplasms on Social Media—#MPNSM

Purpose of review

The use of social media has now become a standard means of communication for many individuals worldwide. The use of one specific form of social media, Twitter, has increased among healthcare providers, both as a means of information gathering and as a conduit for original content creation. Recently, major efforts by users have been put forward to help streamline the unprecedented amount of information that can be found on Twitter. These efforts have led to the creation of diseasespecific hashtag (#) medical communities and have greatly enhanced the ability to understand and better categorize the available data on Twitter. Specifically, for those involved in rare cancer fields, adhering to organically designed and consistently used hashtags has led to the rapid, reliable dissemination of information and the ability to efficiently discuss and debate topics of interest in the field. For the field of myeloproliferative neoplasms (MPNs), the creation of #MPNSM (myeloproliferative neoplasms on social media) in 2015 has facilitated interactions among healthcare stakeholders from all over the world in the MPN field.

Recent findings

In order to better understand the trends and topics of interest to Twitter users of this novel medical community, we conducted the present analysis which focuses on Twitter analytics from the first two years of #MPNSM.

Summary

In this analysis, we observed a sustained increase in the number of Twitter users, number of tweets, number of impressions, and number of retweets over time, demonstrating the feasibility of creating and maintaining a disease-specific hashtag for a rare cancer over time.

     

Conditions for Autonomous Choice - a Qualitative Study of Older Adults’ Experience of Decision-making in Trans-catheter Aortic Valve Replacement (TAVR)

Background Patient autonomy is a leading principle in bioethics and a basis for shared decision making. This study explores conditions for an autonomous choice experienced by older adults who recently underwent trans-catheter aortic valve replacement (TAVR). Methods Qualitative study entailing semi-structured interviews of a purposive sample of ten older (range 73–89, median 83.5 years) adults after TAVR (median 23 days). The study setting was a cardiac department at a university hospital performing TAVR since 2010. Analysis was by systematic text condensation. Results Even when choice seemed hard or absent, TAVR-patients deliberately took the chance offered them by processing risk assessment, ambivalence and fate. They regarded declining the treatment to be worse than accepting the risk related to the procedure. The experience of being thoroughly advised by their physician formed the basis of an autonomous trust. The trust they felt for the physicians’ recommendations mitigated ambivalence about the procedure and risks. TAVR patients expressed feelings consistent with self-empowerment and claimed that it had to be their decision. Even so, choosing the intervention as an obligation to their family or passively accepting it was also reported. Conclusions Older TAVR patients’ experience of an autonomous decision may encompass frank tradeoff; deliberate physician dependency as well as a resilient self-view. Physicians should be especially aware of how older adults’ subtle cognitive declines and inclinations to preserve their identities which can influence their medical decision making when obtaining informed consent. Cardiologists and other providers may also use these insights to develop new strategies that better respond to such inherent complexities.     

Performance of long-term CT monitoring in diagnosing bronchiolitis obliterans after lung transplantation

AIM: The purpose of the study was to evaluate the ability of CT, including expiratory scans with minimum intensity projection in predicting the development of bronchiolitis obliterans syndrome after lung transplantation. MATERIALS AND METHODS: Forty consecutive patients, 29 bilateral and 11 single lung transplanted, were followed-up with regular scans for a median of 36 months. Air trapping was evaluated on expiratory scans constructed from two short spiral scans with minimum intensity projection-technique, one at the level of the carina and the other midway between the right diaphragm and the carina. Air trapping was scored on a 16-point scale. Bronchiolitis obliterans syndrome was diagnosed according to established clinical criteria and quantified spirometrically. RESULTS: Bronchiolitis obliterans syndrome developed in 17 patients (43%) after a median of 12 months. Air trapping and bronchiectasis was seen before the diagnosis of bronchiolitis obliterans syndrome in only two and one patient, respectively. Interobserver agreement for air trapping score was good (kappa = 0.65). Air trapping scores performed significantly better than that achieved by chance alone in determining the presence of bronchiolitis obliterans syndrome (P = 0.0025). An air trapping score of 4 or more provided the best results with regard to sensitivity and specificity in diagnosing bronchiolitis obliterans syndrome. The sensitivity, specificity, positive and negative predictive values of an air trapping of 4 or more in the diagnosis of bronchiolitis obliterans syndrome were 77, 74, 68 and 81%, respectively. CONCLUSION: Expiratory CT scans with minimum intensity projection-reconstruction did not predict the development of bronchiolitis obliterans syndrome in most patients. The findings seriously limit the clinical usefulness of long-term CT monitoring for diagnosing bronchiolitis obliterans syndrome after lung transplantation.     

Four Human Cases of Eastern Equine Encephalitis in Connecticut,USA, during a Larger Regional Outbreak, 2019

During 3 weeks in 2019, 4 human cases of Eastern equine encephalitis (EEE) were diagnosed at a single hospital in Connecticut, USA. The cases coincided with notable shifts in vector–host infection patterns in the northeastern United States and signified a striking change in EEE incidence. All 4 cases were geographically clustered, rapidly progressive, and neurologically devastating. Diagnostic tests conducted by a national commercial reference laboratory revealed initial granulocytic cerebrospinal fluid pleocytosis and false-negative antibody results. EEE virus infection was diagnosed only after patient samples were retested by the arbovirus laboratory of the Centers for Disease Control and Prevention in Fort Collins, Colorado, USA. The crucial diagnostic challenges, clinical findings, and epidemiologic patterns revealed in this outbreak can inform future public health and clinical practice.