Carriage of upper respiratory tract pathogens in rural communities of Sarawak, Malaysian Borneo.

INTRODUCTION: Pneumonia is a leading cause of death in Malaysia. Whilst many studies have reported the aetiology of pneumonia in Western countries, the epidemiology of pneumonia in Malaysia remains poorly understood. As carriage is a prerequisite for disease, we sought to improve our understanding of the carriage and antimicrobial resistance (AMR) of respiratory tract pathogens in Malaysia. The rural communities of Sarawak are an understudied part of the Malaysian population and were the focus of this study, allowing us to gain a better understanding of bacterial epidemiology in this population. METHODS: A population-based survey of bacterial carriage was undertaken in participants of all ages from rural communities in Sarawak, Malaysia. Nasopharyngeal, nasal, mouth and oropharyngeal swabs were taken. Bacteria were isolated from each swab and identified by culture-based methods and antimicrobial susceptibility testing conducted by disk diffusion or E test. RESULTS: 140 participants were recruited from five rural communities. Klebsiella pneumoniae was most commonly isolated from participants (30.0%), followed by Staphylococcus aureus (20.7%), Streptococcus pneumoniae (10.7%), Haemophilus influenzae (9.3%), Moraxella catarrhalis (6.4%), Pseudomonas aeruginosa (6.4%) and Neisseria meningitidis (5.0%). Of the 21 S. pneumoniae isolated, 33.3 and 14.3% were serotypes included in the 13 valent PCV (PCV13) and 10 valent PCV (PCV10) respectively. 33.8% of all species were resistant to at least one antibiotic, however all bacterial species except S. pneumoniae were susceptible to at least one type of antibiotic. CONCLUSION: To our knowledge, this is the first bacterial carriage study undertaken in East Malaysia. We provide valuable and timely data regarding the epidemiology and AMR of respiratory pathogens commonly associated with pneumonia. Further surveillance in Malaysia is necessary to monitor changes in the carriage prevalence of upper respiratory tract pathogens and the emergence of AMR, particularly as PCV is added to the National Immunisation Programme (NIP).

Pneumococcal conjugate vaccine implementation in middle-income countries.

BACKGROUND: Since 2000, the widespread adoption of pneumococcal conjugate vaccines (PCVs) has had a major impact in the prevention of pneumonia. Limited access to international financial support means some middle-income countries (MICs) are trailing in the widespread use of PCVs. We review the status of PCV implementation, and discuss any needs and gaps related to low levels of PCV implementation in MICs, with analysis of possible solutions to strengthen the PCV implementation process in MICs. MAIN BODY: We searched PubMed, PubMed Central, Ovid MEDLINE, and SCOPUS databases using search terms related to pneumococcal immunization, governmental health policy or programmes, and MICs. Two authors independently reviewed the full text of the references, which were assessed for eligibility using pre-defined inclusion and exclusion criteria. The search terms identified 1,165 articles and the full texts of 21 were assessed for suitability, with eight articles included in the systematic review. MICs are implementing PCVs at a slower rate than donor-funded low-income countries and wealthier developed countries. A significant difference in the uptake of PCV in lower middle-income countries (LMICs) (71%) and upper middle-income countries (UMICs) (48%) is largely due to an unsuccessful process of "graduation" of MICs from GAVI assistance, an issue that arises as countries cross the income eligibility threshold and are no longer eligible to receive the same levels of financial assistance. A lack of country-specific data on disease burden, a lack of local expertise in economic evaluation, and the cost of PCV were identified as the leading causes of the slow uptake of PCVs in MICs. Potential solutions mentioned in the reviewed papers include the use of vaccine cost-effectiveness analysis and the provision of economic evidence to strengthen decision-making, the evaluation of the burden of disease, and post-introduction surveillance to monitor vaccine impact. CONCLUSION: The global community needs to recognise the impediments to vaccine introduction into MICs. Improving PCV access could help decrease the incidence of pneumonia and reduce the selection pressure for pneumococcal antimicrobial resistance.

Ultrastructural and biochemical characterization of mechanically adaptable collagenous structures in the edible sea urchin Paracentrotus lividus.

The viscoelastic properties of vertebrate connective tissues rarely undergo significant changes within physiological timescales, the only major exception being the reversible destiffening of the mammalian uterine cervix at the end of pregnancy. In contrast to this, the connective tissues of echinoderms (sea urchins, starfish, sea cucumbers, etc.) can switch reversibly between stiff and compliant conditions in timescales of around a second to minutes. Elucidation of the molecular mechanism underlying such mutability has implications for the zoological, ecological and evolutionary field. Important information could also arise for veterinary and biomedical sciences, particularly regarding the pathological plasticization or stiffening of connective tissue structures. In the present investigation we analyzed aspects of the ultrastructure and biochemistry in two representative models, the compass depressor ligament and the peristomial membrane of the edible sea urchin Paracentrotus lividus, compared in three different mechanical states. The results provide further evidence that the mechanical adaptability of echinoderm connective tissues does not necessarily imply changes in the collagen fibrils themselves. The higher glycosaminoglycan (GAG) content registered in the peristomial membrane with respect to the compass depressor ligament suggests a diverse role of these molecules in the two mutable collagenous tissues. The possible involvement of GAG in the mutability phenomenon will need further clarification. During the shift from a compliant to a standard condition, significant changes in GAG content were detected only in the compass depressor ligament. Similarities in terms of ultrastructure (collagen fibrillar assembling) and biochemistry (two alpha chains) were found between the two models and mammalian collagen. Nevertheless, differences in collagen immunoreactivity, alpha chain migration on SDS-PAGE and BLAST alignment highlighted the uniqueness of sea urchin collagen with respect to mammalian collagen.

Mechanical properties of the compass depressors of the sea-urchin Paracentrotus lividus (Echinodermata, Echinoidea) and the effects of enzymes, neurotransmitters and synthetic tensilin-like protein.

The compass depressors (CDs) of the sea-urchin lantern are ligaments consisting mainly of discontinuous collagen fibrils associated with a small population of myocytes. They are mutable collagenous structures, which can change their mechanical properties rapidly and reversibly under nervous control. The aims of this investigation were to characterise the baseline (i.e. unmanipulated) static mechanical properties of the CDs of Paracentrotus lividus by means of creep tests and incremental force-extension tests, and to determine the effects on their mechanical behaviour of a range of agents. Under constant load the CDs exhibited a three-phase creep curve, the mean coefficient of viscosity being 561±365 MPa.s. The stress-strain curve showed toe, linear and yield regions; the mean strain at the toe-linear inflection was 0.86±0.61; the mean Young's modulus was 18.62±10.30 MPa; and the mean tensile strength was 8.14±5.73 MPa. Hyaluronidase from Streptomyces hyalurolyticus had no effect on creep behaviour, whilst chondroitinase ABC prolonged primary creep but had no effect on secondary creep or on any force-extension parameters; it thus appears that neither hyaluronic acid nor sulphated glycosaminoglycans have an interfibrillar load transfer function in the CD. Acetylcholine, the muscarinic agonists arecoline and methacholine, and the nicotinic agonists nicotine and 1-[1-(3,4-dimethyl-phenyl)-ethyl]-piperazine produced an abrupt increase in CD viscosity; the CDs were not differentially sensitive to muscarinic or nicotinic agonists. CDs showed either no, or no consistent, response to adrenaline, L-glutamic acid, 5-hydroxytryptamine and γ-aminobutyric acid. Synthetic echinoid tensilin-like protein had a weak and inconsistent stiffening effect, indicating that, in contrast to holothurian tensilins, the echinoid molecule may not be involved in the regulation of collagenous tissue tensility. We compare in detail the mechanical behaviour of the CD with that of mammalian tendon and highlight its potential as a model system for investigating poorly understood aspects of the ontogeny and phylogeny of vertebrate collagenous tissues.

Comparing dynamic connective tissue in echinoderms and sponges: morphological and mechanical aspects and environmental sensitivity.

Echinoderms and sponges share a unique feature that helps them face predators and other environmental pressures. They both possess collagenous tissues with adaptable viscoelastic properties. In terms of morphology these structures are typical connective tissues containing collagen fibrils, fibroblast- and fibroclast-like cells, as well as unusual components such as, in echinoderms, neurosecretory-like cells that receive motor innervation. The mechanisms underpinning the adaptability of these tissues are not completely understood. Biomechanical changes can lead to an abrupt increase in stiffness (increasing protection against predation) or to the detachment of body parts (in response to a predator or to adverse environmental conditions) that are regenerated. Apart from these advantages, the responsiveness of echinoderm and sponge collagenous tissues to ionic composition and temperature makes them potentially vulnerable to global environmental changes.