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The Lancet. Microbe May 2024Streptococcus pyogenes causes more than 500 000 deaths per year globally, which occur disproportionately in low-income and middle-income countries. The roles of S...
BACKGROUND
Streptococcus pyogenes causes more than 500 000 deaths per year globally, which occur disproportionately in low-income and middle-income countries. The roles of S pyogenes skin and pharyngeal carriage in transmission are unclear. We aimed to investigate the clinical epidemiology and household transmission dynamics of both S pyogenes asymptomatic carriage and infection in a high-burden setting.
METHODS
We did a 1-year prospective, longitudinal, household cohort study, recruiting healthy participants from households in Sukuta, The Gambia. Households were eligible if they comprised at least three members, including one child younger than 18 years, and were excluded if more than half of household members declined to participate. Households were identified by random GPS coordinates derived from census data. At monthly visits, pharyngeal and normal skin swabs were collected for S pyogenes culture, and sociodemographic data were recorded by interview. Incident pharyngitis and pyoderma infections were captured. Cultured isolates underwent emm genotyping. The primary outcome measures were incidence of S pyogenes carriage and disease. Additional outcomes were prevalence of S pyogenes skin and pharyngeal carriage, S pyogenes skin and pharyngeal clearance time, S pyogenes emm type, risk factors for carriage and disease events, household secondary attack rate, and emm-linked household transmission events. The study is registered on ClinicalTrials.gov, NCT05117528.
FINDINGS
Between July 27, 2021, and Sept 28, 2022, 442 participants were enrolled from 44 households. The median age was 15 years (IQR 6-28) and 233 (53%) were female. We identified 17 pharyngitis and 99 pyoderma events and 49 pharyngeal and 39 skin S pyogenes carriage acquisition events. Mean monthly prevalence was 1·4% (95% CI 1·1-1·9) for S pyogenes pharyngeal carriage and 1·2% (0·9-1·6) for S pyogenes skin carriage. Incidence was 120 per 1000 person-years (95% CI 87-166) for S pyogenes pharyngeal carriage, 124 per 1000 person-years (90-170) for S pyogenes skin carriage, 51 per 1000 person-years (31-84) for S pyogenes pharyngitis, and 263 per 1000 person-years (212-327) for S pyogenes pyoderma. Pharyngeal carriage risk was higher during the rainy season (HR 5·67, 95% CI 2·19-14·69) and in larger households (per additional person: 1·03, 1·00-1·05), as was pharyngitis risk (rainy season: 3·00, 1·10-8·22; household size: 1·04, 1·02-1·07). Skin carriage risk was not affected by season or household size, but was lower in female than in male participants (0·45, 0·22-0·92) and highest in children younger than 5 years compared with adults (22·69, 3·08-167·21), with similar findings for pyoderma (female sex: 0·34, 0·19-0·61; age <5 years: 7·00, 2·78-17·64). Median clearance time after carriage acquisition was 4·0 days for both skin (IQR 3·5-7·0) and pharynx (3·5-7·3). The mean household secondary attack rate was 4·9 (95% CI 3·5-6·3) for epidemiologically linked S pyogenes events and 0·74 (0·3-1·2) for emm-linked S pyogenes events. Of the 204 carriage and disease events, emm types were available for 179 (88%). Only 18 emm-linked between-visit household transmission events were identified. Pyoderma was the most common source of S pyogenes household transmissions in 11 (61%) of 18 emm-linked transmissions. Both pharynx to skin and skin to pharynx transmission events were observed.
INTERPRETATION
S pyogenes carriage and infection are common in The Gambia, particularly in children. Most events are non-household acquisitions, but skin carriage and pyoderma have an important role in S pyogenes household transmission and bidirectional transmission between skin and pharynx occurs.
FUNDING
Wellcome Trust, Chadwick Trust, Fonds National de la Recherche Scientifique (Belgium), European Society for Paediatric Infectious Diseases, and Medical Research Council (UK).
PubMed: 38735305
DOI: 10.1016/S2666-5247(24)00046-6 -
International Journal of Dermatology May 2024
PubMed: 38727093
DOI: 10.1111/ijd.17200 -
Cureus Apr 2024Pyoderma Gangrenosum (PG) is a distinctive dermatologic condition characterized by recurrent inflammatory ulcers, often manifesting with violaceous borders and...
Pyoderma Gangrenosum (PG) is a distinctive dermatologic condition characterized by recurrent inflammatory ulcers, often manifesting with violaceous borders and undermined edges. We describe a 40-year-old male who presented with acute on chronic necrotic ulcer of the left index finger following foreign body penetration. Despite multiple emergency department visits and treatments for presumed recurrent cellulitis, including various debridements, his condition persisted without symptomatic relief. A high index of clinical suspicion, due to recurrent presentations and potential pathergy, prompted an excision biopsy which confirmed Pyoderma Gangrenosum (PG). Regrettably, due to delays in appropriate management, the patient chose amputation because of intolerable pain, highlighting the critical importance of timely diagnosis for optimal patient outcomes.
PubMed: 38716010
DOI: 10.7759/cureus.57762 -
The American Journal of Tropical... Jun 2024The COVID-19 pandemic has altered the epidemiology of many common childhood infections, including Group A streptococcal (GAS) disease. Acute post-streptococcal...
The COVID-19 pandemic has altered the epidemiology of many common childhood infections, including Group A streptococcal (GAS) disease. Acute post-streptococcal glomerulonephritis (APSGN) is a nonsuppurative complication of GAS pharyngitis and pyoderma. It remains the most common cause of pediatric acute glomerulonephritis globally. In Counties Manukau, New Zealand, APSGN rates have previously been shown to be the highest in the country, with marked ethnic and socioeconomic disparities. We performed a retrospective review of children aged 0-14 years who were discharged from Kidz First Hospital, Counties Manukau, between 2015 and 2023 and met the Strep A Vaccine Global Consortium consensus definition of APSGN. We describe a marked, sustained reduction in APSGN hospitalizations, temporally associated with the COVID-19 pandemic. This ongoing reduction in APSGN incidence is notable in light of contrasting reports of increasing incidence of rheumatic fever in New Zealand and invasive GAS disease internationally.
Topics: Humans; New Zealand; COVID-19; Streptococcal Infections; Glomerulonephritis; Child; Child, Preschool; Adolescent; Incidence; Infant; Male; Retrospective Studies; Female; Streptococcus pyogenes; SARS-CoV-2; Infant, Newborn; Hospitalization; Acute Disease
PubMed: 38688264
DOI: 10.4269/ajtmh.23-0762 -
Journal of the American Academy of... Apr 2024
Low incidence of invasive fungal infection and risk factors in a large observational cohort of patients initiating tumor necrosis factor-alpha inhibitors for dermatologic conditions.
PubMed: 38685411
DOI: 10.1016/j.jaad.2024.03.046 -
Cureus Mar 2024Pyoderma gangrenosum (PG) is a rare autoinflammatory neutrophilic dermatosis. The ulcerative subtype presents with a tender nodule or pustule that progresses into a...
Pyoderma gangrenosum (PG) is a rare autoinflammatory neutrophilic dermatosis. The ulcerative subtype presents with a tender nodule or pustule that progresses into a painful, necrotic ulcer.New lesions arise after minor trauma in one-third of patients, a phenomenon termed "pathergy." We present a 62-year-old Caucasian female with primary sclerosing cholangitis, hepatic cirrhosis, chronic hepatitis B, and severe PG. At the initial presentation, she had lesions on her face and four extremities. She had severe full-thickness ulcerations on the bilateral cheeks and underwent incision and drainage with washout of bilateral maxillary abscesses, left sinus curettage, and wound debridement. She has required multiple hospitalizations for severe flares. Treatment with steroids was complicated by spinal compression fractures. Steroid-sparring agents were ineffective. Her lesions involved bilateral cheeks, temples, temporal scalp, and eyelids with oroantral fistulae. Her facial ulcerations included a large septal perforation causing saddle nose deformity and eradication of a branch of the left facial nerve causing incomplete eye closure. She underwent bilateral facial wound irrigation with antibiotic irrigation and wound debridement. Due to social factors, she has been lost to follow-up and a definitive etiology of her PG has not yet been elucidated. Although rare, PG should remain a consideration in patients with ulcerative lesions on the head and neck. Wound debridement is typically discouraged given the risk of pathergy, but there may be a role for surgical intervention in adequately immunosuppressed patients.
PubMed: 38681354
DOI: 10.7759/cureus.57136 -
Pharmaceutics Apr 2024The effective pharmacological treatment of inflamed wounds such as pyoderma gangraenosum remains challenging, as the systemic application of suitable drugs such as...
The effective pharmacological treatment of inflamed wounds such as pyoderma gangraenosum remains challenging, as the systemic application of suitable drugs such as glucocorticoids is compromised by severe side effects and the inherent difficulties of wounds as drug targets. Furthermore, conventional semi-solid formulations are not suitable for direct application to open wounds. Thus, the treatment of inflamed wounds could considerably benefit from the development of active wound dressings for the topical administration of anti-inflammatory drugs. Although bacterial cellulose appears to be an ideal candidate for this purpose due to its known suitability for advanced wound care and as a drug delivery system, the incorporation of poorly water-soluble compounds into the hydrophilic material still poses a problem. The use of microemulsions could solve that open issue. The present study therefore explores their use as a novel approach to incorporate poorly water-soluble glucocorticoids into bacterial cellulose. Five microemulsion formulations were loaded with hydrocortisone or dexamethasone and characterized in detail, demonstrating their regular microstructure, biocompatibility and shelf-life stability. Bacterial cellulose was successfully loaded with the formulations as confirmed by transmission electron microscopy and surprisingly showed homogenous incorporation, even of w/o type microemulsions. High and controllable drug permeation through Strat-M membranes was observed, and the anti-inflammatory activity for permeated glucocorticoids was confirmed in vitro. This study presents a novel approach for the development of anti-inflammatory wound dressings using bacterial cellulose in combination with microemulsions.
PubMed: 38675165
DOI: 10.3390/pharmaceutics16040504 -
Antibiotics (Basel, Switzerland) Apr 2024is an opportunistic pathogen commonly found in canines, and has garnered escalating interest due to its potential for zoonotic transmission and increasing antimicrobial...
is an opportunistic pathogen commonly found in canines, and has garnered escalating interest due to its potential for zoonotic transmission and increasing antimicrobial resistance. However, the excessive use of antibiotics and the characteristic of forming biofilms make treatment challenging. In this study, the in vivo and in vitro antimicrobial activity and mechanisms of action of NZ2114, a plectasin-derived peptide, against were investigated. NZ2114 exhibited potent antibacterial activity towards (minimum inhibitory concentration, MIC = 0.23 μM) with a lower probability of inducing drug-resistant mutations and efficient bactericidal action, which was superior to those of mopirucin (MIC = 0.25-0.5 μM) and lincomycin (MIC = 4.34-69.41 μM). The results of electron microscopy and flow cytometry showed that NZ2114 disrupted cell membrane, resulting in cellular content leakage, cytoplasmic membrane shrinkage, and, eventually, cell death. The intracellular ROS activity and Alamar Blue detection showed that NZ2114 interferes with intracellular metabolic processes. In addition, NZ2114 effectively inhibits biofilm formation, and confocal laser scanning microscopy further revealed its antibacterial and anti-biofilm activity (biofilm thickness reduced to 6.90-17.70 μm). The in vivo therapy of NZ2114 in a mouse pyoderma model showed that it was better than lincomycin in effectively decreasing the number of skin bacteria, alleviating histological damage, and reducing the skin damage area. These results demonstrated that NZ2114 may be a promising antibacterial candidate against infections.
PubMed: 38667017
DOI: 10.3390/antibiotics13040341 -
Clinical and Experimental Dermatology Apr 2024Pyoderma gangrenosum (PG) is an ulcerative inflammatory disorder affecting the lower legs in 80% of cases. The use of biologic medications to treat PG is increasing...
Current prescribing for pyoderma gangrenosum in the UK and access to biologic medications: Results from a UK Dermatology Clinical Trials Network (UKDCTN) survey of UK Dermatologists.
Pyoderma gangrenosum (PG) is an ulcerative inflammatory disorder affecting the lower legs in 80% of cases. The use of biologic medications to treat PG is increasing although there is a limited evidence base to guide treatment choices. In some health systems, such as the UK NHS, limitations are placed on biologic prescribing for PG leading to wide variations in prescribing. A survey of mainly UK clinicians showed that prednisolone remains the first line treatment for PG (90%). Biologics have been used by 66% of clinicians as second line therapy but 19% have had prescribing requests declined. Further research is needed to determine optimal treatment strategies for PG.
PubMed: 38661219
DOI: 10.1093/ced/llae153 -
The International Journal of Lower... Apr 2024Chronic wounds have long been a significant public health concern, but the true impact of these wounds is unknown since research designs and measuring techniques vary,... (Review)
Review
Chronic wounds have long been a significant public health concern, but the true impact of these wounds is unknown since research designs and measuring techniques vary, leading to inconsistent estimates. The definition of a wound is a loss of epithelial continuity caused by damage to the tissue. The following conditions can cause chronic wounds: panniculitis, pyoderma gangrenosum, traumatic, neurological, metabolic, hematologic, neoplastic, or infection-related. The growing global incidence of diabetes and the aging population necessitate greater attention to chronic wounds. Regrettably, it is sad that significant healthcare institutions have overlooked wound research. The study of health-related illnesses and occurrences in particular populations, including their distribution, frequency, and determinants, and the application of this research to control health problems.
PubMed: 38659348
DOI: 10.1177/15347346241246339