Epidemiology and economic burden of meningococcal disease in Germany: A systematic review.

INTRODUCTION: Invasive meningococcal disease (IMD) is a notifiable disease in Germany and other European countries. Due to the high lethality of the disease and the risk of long-term consequences, IMD prevention is of high public health relevance despite the low number of cases in the population. This study aims to describe key epidemiological and economic parameters of IMD in Germany to support national decision-making processes for implementing enhanced prevention measures. METHODS: Based on a systematic literature review in PubMed and EMBASE, all publications on the burden of disease and costs of IMD published up to May 2020 were evaluated. Additionally, notification data were used to report the annual case numbers and incidence of IMD in Germany until the end of 2019. RESULTS: Thirty-six studies were included, of which 35 reported data on the epidemiological burden of disease and three reported data on economic aspects of IMD. The type of reported endpoints and results on the incidence of IMD differed widely by reporting year, population, and data source used. Most of the data are reported without specific information about a serogroup. Data on the economic burden of disease and healthcare resource use are scarce. Based on mandatory notification data, a decrease in the incidence of notified IMD cases has been observed since 2004. Currently, the nationwide annual incidence in Germany is at 0.3 cases per 100,000 persons and has gradually decreased. While the overall decline is mainly attributable to MenB, cases with MenY and MenW are the only ones that have increased on a low level in recent years. CONCLUSION: While IMD is a rare disease, high direct and indirect costs illustrate the relevance of the disease for patients, caregivers, as well as for the health care system. Future research should concentrate on quantifying the long-term economic burden and indirect costs of meningococcal disease. Integrated IMD surveillance with isolate characterisation remains crucial to inform public health policies.

A three-leg model producing tetrapod and tripod coordination patterns of ipsilateral legs in the stick insect.

Insect locomotion requires the precise coordination of the movement of all six legs. Detailed investigations have revealed that the movement of the legs is controlled by local dedicated neuronal networks, which interact to produce walking of the animal. The stick insect is well suited to experimental investigations aimed at understanding the mechanisms of insect locomotion. Beside the experimental approach, models have also been constructed to elucidate those mechanisms. Here, we describe a model that replicates both the tetrapod and tripod coordination pattern of three ipsilateral legs. The model is based on an earlier insect leg model, which includes the three main leg joints, three antagonistic muscle pairs, and their local neuronal control networks. These networks are coupled via angular signals to establish intraleg coordination of the three neuromuscular systems during locomotion. In the present three-leg model, we coupled three such leg models, representing front, middle, and hind leg, in this way. The coupling was between the levator-depressor local control networks of the three legs. The model could successfully simulate tetrapod and tripod coordination patterns, as well as the transition between them. The simulations showed that for the interleg coordination during tripod, the position signals of the levator-depressor neuromuscular systems sent between the legs were sufficient, while in tetrapod, additional information on the angular velocities in the same system was necessary, and together with the position information also sufficient. We therefore suggest that, during stepping, the connections between the levator-depressor neuromuscular systems of the different legs are of primary importance.

A network model comprising 4 segmental, interconnected ganglia, and its application to simulate multi-legged locomotion in crustaceans.

Inter-segmental coordination is crucial for the locomotion of animals. Arthropods show high variability of leg numbers, from 6 in insects up to 750 legs in millipedes. Despite this fact, the anatomical and functional organization of their nervous systems show basic similarities. The main similarities are the segmental organization, and the way the function of the segmental units is coordinated. We set out to construct a model that could describe locomotion (walking) in animals with more than 6 legs, as well as in 6-legged animals (insects). To this end, we extended a network model by Daun-Gruhn and Tóth (Journal of Computational Neuroscience, doi: 10.1007/s10827-010-0300-1 , 2011). This model describes inter-segmental coordination of the ipsilateral legs in the stick insect during walking. Including an additional segment (local network) into the original model, we could simulate coordination patterns that occur in animals walking on eight legs (e.g., crayfish). We could improve the model by modifying its original cyclic connection topology. In all model variants, the phase relations between the afferent segmental excitatory sensory signals and the oscillatory activity of the segmental networks played a crucial role. Our results stress the importance of this sensory input on the generation of different stable coordination patterns. The simulations confirmed that using the modified connection topology, the flexibility of the model behaviour increased, meaning that changing a single phase parameter, i.e., gating properties of just one afferent sensory signal was sufficient to reproduce all coordination patterns seen in the experiments.

A neuromechanical model for the neuronal basis of curve walking in the stick insect.

The coordination of the movement of single and multiple limbs is essential for the generation of locomotion. Movement about single joints and the resulting stepping patterns are usually generated by the activity of antagonistic muscle pairs. In the stick insect, the three major muscle pairs of a leg are the protractor and retractor coxae, the levator and depressor trochanteris, and the flexor and extensor tibiae. The protractor and retractor move the coxa, and thereby the leg, forward and backward. The levator and depressor move the femur up and down. The flexor flexes, and the extensor extends the tibia about the femur-tibia joint. The underlying neuronal mechanisms for a forward stepping middle leg have been thoroughly investigated in experimental and theoretical studies. However, the details of the neuronal and mechanical mechanisms driving a stepping single leg in situations other than forward walking remain largely unknown. Here, we present a neuromechanical model of the coupled three joint control system of the stick insect's middle leg. The model can generate forward, backward, or sideward stepping. Switching between them is achieved by changing only a few central signals controlling the neuromechanical model. In kinematic simulations, we are able to generate curve walking with two different mechanisms. In the first, the inner middle leg is switched from forward to sideward and in the second to backward stepping. Both are observed in the behaving animal, and in the model and animal alike, backward stepping of the inner middle leg produces tighter turns than sideward stepping.

A neuromechanical model explaining forward and backward stepping in the stick insect.

The mechanism underlying the generation of stepping has been the object of intensive studies. Stepping involves the coordinated movement of different leg joints and is, in the case of insects, produced by antagonistic muscle pairs. In the stick insect, the coordinated actions of three such antagonistic muscle pairs produce leg movements and determine the stepping pattern of the limb. The activity of the muscles is controlled by the nervous system as a whole and more specifically by local neuronal networks for each muscle pair. While many basic properties of these control mechanisms have been uncovered, some important details of their interactions in various physiological conditions have so far remained unknown. In this study, we present a neuromechanical model of the coupled protractor-retractor and levator-depressor neuromuscular systems and use it to elucidate details of their coordinated actions during forward and backward walking. The switch from protraction to retraction is evoked at a critical angle of the femur during downward movement. This angle represents a sensory input that integrates load, motion, and ground contact. Using the model, we can make detailed suggestions as to how rhythmic stepping might be generated by the central pattern generators of the local neuronal networks, how this activity might be transmitted to the corresponding motoneurons, and how the latter might control the activity of the related muscles. The entirety of these processes yields the coordinated interaction between neuronal and mechanical parts of the system. Moreover, we put forward a mechanism by which motoneuron activity could be modified by a premotor network and suggest that this mechanism might serve as a basis for fast adaptive behavior, like switches between forward and backward stepping, which occur, for example, during curve walking, and especially sharp turning, of insects.

Unilateral spatial neglect and defective performance in one half of space.

The performance of 80 unselected patients with unilateral cerebral lesions (verified by CT scan) was compared with that of 34 control subjects on 6 "screening" tests for visual, auditory, tactile, kinaesthetic, motor and conceptual neglect. The performance of all 114 patients was tested comparably on the left and right sides, and (except for motor neglect) also centrally. Cut-off scores were determined so that performance inferior to 95% of the control range could be identified. The criterion for neglect was contralateral defect in the absence of ipsilateral and of central defect. With this procedure 30 patients were identified as showing neglect (5 visual, 6 auditory, 5 tactile and 4 motor--all 20 patients showing only one form of neglect; 10 with various combinations of neglect). In 27 of these 30 patients the lesion was found to be right-sided. The performance of various groups of patients with neglect was then compared with that of the 50 patients without neglect on 26 "evaluative" tests, designed to characterize the different varieties of neglect. For this comparison discriminant analysis was used. The outcome of two discriminant analyses instance a patient with visual and auditory neglect is not similar to a patient either with exclusively visual or with exclusively auditory neglect; (2) mixed, tactile and motor neglect are easy to discriminate from other kinds of neglect, whereas visual and auditory neglect are less easy to discriminate, particularly from patients without neglect; (3) the discriminant functions seem to reflect general spatial defect not confined to one side of space; differential spatial performance to the contralateral/ipsilateral sides; and manipulation. The findings are discussed in relation to previous interpretations of neglect; the defect is regarded as one of local attention.