by Shakirat A. Adetunji, Gilbert Ramirez, Margaret J. Foster, Angela A. M. Arenas-Gamboa

Background

Infection of bones and joints remains one of the most commonly described complications of brucellosis in humans and is predominantly reported in all ages and sexes in high-risk regions, such as the Middle East, Asia, South and Central America, and Africa. We aimed to systematically review the literature and perform a meta-analysis to estimate the global prevalence of osteoarticular brucellosis.

Methodology

Major bibliographic databases were searched using keywords and suitable combinations. All studies reporting the incidence and clinical manifestations of osteoarticular brucellosis in humans, and demonstrated by two or more diagnostic methods (bacteriological, molecular, serological, and/or radiographic) were included. Random effect model was used, and statistical significance was set at 0.5%

Principal findings

A total of 56 studies met the inclusion criteria and were included in the systematic review and meta-analysis. There was an evidence of geographical variation in the prevalence of osteoarticular disease with estimates ranging from 27% in low-risk regions to 36% in high-risk regions. However, the difference was not significant. Thus, brucellosis patients have at least 27% chance of developing osteoarticular disease.

Conclusions

The prevalence of OAB is not dependent on the endemicity of brucellosis in a particular region. Hence, further research should investigate the potential mechanisms of OAB, as well as the influence of age, gender, and other socioeconomic factor variations in its global prevalence, as this may provide insight into associated exposure risks and management of the disease.

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by Eduardo de la Torre-Escudero, Jared Q. Gerlach, Adam P. S. Bennett, Krystyna Cwiklinski, Heather L. Jewhurst, Kathryn M. Huson, Lokesh Joshi, Michelle Kilcoyne, Sandra O’Neill, John P. Dalton, Mark W. Robinson

Helminth parasites secrete extracellular vesicles (EVs) that can be internalised by host immune cells resulting in modulation of host immunity. While the molecular cargo of EVs have been characterised in many parasites, little is known about the surface-exposed molecules that participate in ligand-receptor interactions with the host cell surface to initiate vesicle docking and subsequent internalisation. Using a membrane-impermeable biotin reagent to capture proteins displayed on the outer membrane surface of two EV sub-populations (termed 15k and 120k EVs) released by adult F. hepatica, we describe 380 surface proteins including an array of virulence factors, membrane transport proteins and molecules involved in EV biogenesis/trafficking. Proteomics and immunohistochemical analysis show that the 120k EVs have an endosomal origin and may be released from the parasite via the protonephridial (excretory) system whilst the larger 15k EVs are released from the gastrodermal epithelial cells that line the fluke gut. A parallel lectin microarray strategy was used to profile the topology of major surface oligosaccharides of intact fluorogenically-labelled EVs as they would be displayed to the host. Lectin profiles corresponding to glycoconjugates exposed on the surface of the 15 K and 120K EV sub-populations are practically identical but are distinct from those of the parasite surface tegument, although all are predominated by high mannose sugars. We found that while the F. hepatica EVs were resistant to exo– and endo-glycosidases, the glyco-amidase PNGase F drastically remodelled the surface oligosaccharides and blocked the uptake of EVs by host macrophages. In contrast, pre-treatment with antibodies obtained from infected hosts, or purified antibodies raised against the extracellular domains of specific EV surface proteins (DM9-containing protein, CD63 receptor and myoferlin), significantly enhanced their cellular internalisation. This work highlights the diversity of EV biogenesis and trafficking pathways used by F. hepatica and sheds light on the molecular interaction between parasite EVs and host cells.

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by Felipe Silva-de-França, Isadora Maria Villas-Boas, Solange Maria de Toledo Serrano, Bruno Cogliati, Sonia Aparecida de Andrade Chudzinski, Priscila Hess Lopes, Eduardo Shigueo Kitano, Cinthya Kimori Okamoto, Denise V. Tambourgi

Background

Naja annulifera is a medically important venomous snake occurring in some of the countries in Sub-Saharan Africa. Accidental bites result in severe coagulation disturbances, systemic inflammation and heart damage, as reported in dogs, and death, by respiratory arrest, in humans. Despite the medical importance of N. annulifera, little is known about its venom composition and the pathogenesis of envenomation. In this paper, the toxic, inflammatory and immunogenic properties of N. annulifera venom were analyzed.

Methodology/Principal findings

Venom proteomic analysis identified 79 different proteins, including Three Finger Toxins, Cysteine Rich Secretory Proteins, Metalloproteinases, Phospholipases A₂ (PLA₂), Hyaluronidase, L-amino-acid oxidase, Cobra Venom Factor and Serine Proteinase. The presence of PLA₂, hyaluronidase, fibrinogenolytic and anticoagulant activities was detected using functional assays. The venom was cytotoxic to human keratinocytes. In an experimental murine model of envenomation, it was found that the venom induced local changes, such as swelling, which was controlled by anti-inflammatory drugs. Moreover, the venom caused death, which was preceded by systemic inflammation and pulmonary hemorrhage. The venom was shown to be immunogenic, inducing a strong humoral immune response, with the production of antibodies able to recognize venom components with high molecular weight and to neutralize its lethal activity.

Conclusions/Significance

The results obtained in this study demonstrate that N. annulifera venom contains toxins able to induce local and systemic inflammation, which can contribute to lung damage and death. Moreover, the venom is immunogenic, an important feature that must be considered during the production of a therapeutic anti-N. annulifera antivenom.

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