Neglected Zoonotic Diseases—The Long and Winding Road to Advocacy

Mableson, Hayley; Okello, Anna; Picozzi, Kim; Welburn, Susan C.

doi:10.1371/journal.pntd.0002800

Cited by 86 publications

(75 citation statements)

References 6 publications

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“…Transmission to humans typically occurs through the consumption of unpasteurized dairy products or via aerosol following contact with contaminated meat products (3,4). Although vaccination of livestock has reduced disease incidence, no licensed human vaccine is available, and brucellosis has recently been designated a neglected zoonotic disease by the World Health Organization (5,6). Osteoarticular and musculoskeletal inflammation are the most common focal complications of human brucellosis and occur in 40 to 80% of Brucella-infected patients (7,8).…”

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confidence: 99%

Temporal Role for MyD88 in a Model of Brucella-Induced Arthritis and Musculoskeletal Inflammation

et al. 2017

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Brucella spp. are facultative intracellular Gram-negative bacteria that cause the zoonotic disease brucellosis, one of the most common global zoonoses. Osteomyelitis, arthritis, and musculoskeletal inflammation are common focal complications of brucellosis in humans; however, wild-type (WT) mice infected systemically with conventional doses of Brucella do not develop these complications. Here we report C57BL/6 WT mice infected via the footpad with 10 3 to 10 6 CFU of Brucella spp. display neutrophil and monocyte infiltration of the joint space and surrounding musculoskeletal tissue. Joint inflammation is detectable as early as 1 day postinfection and peaks 1 to 2 weeks later, after which WT mice are able to slowly resolve inflammation. B and T cells were dispensable for the onset of swelling but required for resolution of joint inflammation and infection. At early time points, MyD88 Ϫ/Ϫ mice display decreased joint inflammation, swelling, and proinflammatory cytokine levels relative to WT mice. Subsequently, swelling of MyD88 Ϫ/Ϫ joints surpassed WT joint swelling, and resolution of joint inflammation was prolonged. Joint bacterial loads in MyD88 Ϫ/Ϫ mice were significantly greater than those in WT mice by day 3 postinfection and at all time points thereafter. In addition, MyD88 Ϫ/Ϫ joint inflammatory cytokine levels on day 3 and beyond were similar to WT levels. Collectively these data demonstrate MyD88 signaling mediates early inflammatory responses in the joint but also contributes to subsequent clearance of Brucella and resolution of inflammation. This work also establishes a mouse model for studying Brucellainduced arthritis, musculoskeletal complications, and systemic responses, which will lead to a better understanding of focal complications of brucellosis.KEYWORDS arthritis, osteomyelitis, Brucella, brucellosis, MyD88, musculoskeletal B rucella spp. infect over 500,000 individuals each year, making brucellosis one of the most common global zoonoses (1). The most prevalent species that infect humans are Brucella melitensis, Brucella abortus, and Brucella suis (2). Transmission to humans typically occurs through the consumption of unpasteurized dairy products or via aerosol following contact with contaminated meat products (3, 4). Although vaccination of livestock has reduced disease incidence, no licensed human vaccine is available, and brucellosis has recently been designated a neglected zoonotic disease by the World Health Organization (5, 6). Osteoarticular and musculoskeletal inflammation are the most common focal complications of human brucellosis and occur in 40 to 80% of Brucella-infected patients (7,8). This arthritis is thought to arise from the hematogenous spread of Brucella to the joints, as viable brucellae can be found within the synovial fluid of infected patients (9, 10). Arthritis can manifest as peripheral arthritis, sacroiliitis, and spondylitis, which are most common in children, young adults and older adults, respectively (7,8,11,12). Inflammation of the joint synovium is pre...

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Temporal Role for MyD88 in a Model of Brucella-Induced Arthritis and Musculoskeletal Inflammation

et al. 2017

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“…Brucellosis is endemic in several regions of the world, with more than 500,000 new cases each year (2)(3)(4)(5). To date, 10 recognized species of Brucella have been described, with the most pathogenic for humans being Brucella melitensis (2).…”

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A Simple and Safe Protocol for Preparing Brucella Samples for Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry Analysis

et al. 2016

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dWe describe a simple protocol to inactivate the biosafety level 3 (BSL3) pathogens Brucella prior to their analysis by matrix-assisted laser desorption ionization-time of flight mass spectrometry. This method is also effective for several other bacterial pathogens and allows storage, and eventually shipping, of inactivated samples; therefore, it might be routinely applied to unidentified bacteria, for the safety of laboratory workers. Brucellosis is a zoonosis caused by bacteria of the genus Brucella, which are transmitted to humans through direct contact, ingestion of contaminated animal products, or aerosolization (1, 2). Brucellosis is endemic in several regions of the world, with more than 500,000 new cases each year (2-5). To date, 10 recognized species of Brucella have been described, with the most pathogenic for humans being Brucella melitensis (2). Diagnoses of clinical brucellosis are made initially using serological tests and are confirmed by isolation of the agent (6, 7). The recent introduction of matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) has revolutionized the identification of bacteria and yeasts (8, 9). However, the procedures recommended by the manufacturers for non-biosafety level 3 (BSL3) organisms are not adequate for the manipulation of Brucella strains, which are classified as BSL3 (potential bioterrorism pathogens) and represent potential health hazards for laboratory workers (1, 10). Any inactivation procedure must allow safe sample handling outside the BSL3 environment and must avoid destruction of the biomarkers used for identification. Therefore, we developed a simple, safe, and efficient sample preparation method for Brucella isolates that is compatible with their analysis by the current MALDI-TOF MS platforms.Solvent inactivation of Brucella. We first applied the direct transfer procedure recommended by the manufacturer to a panel of Brucella strains, working in class II microbiological safety cabinets in a BSL3 laboratory (Table 1). The target plate (Vitek MS DS slide; bioMérieux) was inoculated by picking a portion of a colony from a plate with a 1-l disposable loop (Sarsted), and the deposit was overlaid with 1 l of ␣-cyano-4-hydroxycinnamic acid (CHCA) matrix solution (saturated solution of CHCA in a solvent mixture composed of 33% acetonitrile, 33% absolute ethanol, 3% trifluoroacetic acid, and 31% water) and then air dried for 2 min at room temperature. The dried material was recovered with a sterile swab and spread on culture plates, which were then incubated for up to 3 weeks under the optimal growth conditions for the corresponding bacteria indicated in Table 1. Viable bacteria were recovered for most strains, showing that this protocol does not kill all Brucella strains, possibly because the bacterial deposit was not completely covered with the matrix solution. This risk is not acceptable for BSL3 pathogens. To overcome this problem, different liquid-phase inactivation protocols were tested in 1.5-ml Eppendorf tubes (see F...

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“…Diagnosis may be microbiological, employing traditional methods, such as gram-staining, capsule staining from the smear of the lesion, or culturing of B. anthracis on sheep blood agar (5%) and other routine culture media [8][9][10]. However, despite the existence of many molecular tests for anthrax, these systems are difficult to deploy with available resources in distant locations where anthrax is endemic [11]. Therefore, rapid, user-friendly, inexpensive serodiagnostic tests can be important tools for the surveillance of anthrax, minimizing agriculture-or occupation-related cases.…”

Section: Discussionmentioning

confidence: 99%

“…However, recognition of the public health importance of three major NZDs (anthrax, brucellosis, and bovine tuberculosis) in countries where the diseases are endemic, is still lacking, despite being a WHO priority since as early as the 1950s. Global advocacy for NZD control would similarly benefit from the One Health approach adopted for the NTDs under the WHA [11].…”

Section: Discussionmentioning

confidence: 99%

Diagnosis of cutaneous anthrax in resource-poor settings in West Arsi Province, Ethiopia

Pérez‐Tanoira¹,

Ramos

Prieto-Pérez³

et al. 2017

Ann Agric Environ Med.

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Introduction. Cutaneous anthrax is a zoonotic disease caused by the spore-forming bacterium Bacillus anthracis, which typically presents with ulcers after contact with animals or animal products, and is rarely seen in high-income countries but is common in those with low-and middle-incomes. Objective. The aim of this study is to show the main clinical characteristics of cutaneous anthrax in endemic areas. Materials and method. The study describes the main clinical characteristics of cutaneous anthrax in eight patients (six female and two male, age range 1 -56 years) admitted to the rural General Hospital of Gambo, West Arsi Province of Ethiopia from 2010-2013. Results. In all cases, lesions began as an erythematous papule located on exposed sites (n=7 head; n=1 thigh) and subsequently became a necrotic black eschar surrounded by an edematous halo. Two patients presented with painful ipsilateral adenopathy near the black eschar. Four patients developed a malignant pustule on the suborbital region of the face. Patients responded positively to treatment, and the lesions resolved, leaving eschars. However, one patient suffered the loss of an eyeball, and another died 12 hours after starting treatment. Conclusions. Physicians working in rural areas of resource-poor settings should be trained in the clinical identification of cutaneous anthrax. Early antibiotic treatment is essential for decreasing morbidity and mortality.

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Neglected Zoonotic Diseases—The Long and Winding Road to Advocacy

Cited by 86 publications

References 6 publications

Temporal Role for MyD88 in a Model of Brucella-Induced Arthritis and Musculoskeletal Inflammation

Temporal Role for MyD88 in a Model of Brucella-Induced Arthritis and Musculoskeletal Inflammation

A Simple and Safe Protocol for Preparing Brucella Samples for Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry Analysis

Diagnosis of cutaneous anthrax in resource-poor settings in West Arsi Province, Ethiopia

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