Publications by authors named "Scott Nash"

Background: Trachoma is targeted by the World Health Organization (WHO) for elimination as a public health problem by 2030. Trachoma impact surveys using standardised methodology are recommended to monitor progress towards elimination and to determine eligibility for continued surgery, antibiotics, facial cleanliness, and environmental improvement (SAFE) interventions. From 2007 to 2015, four counties of Eastern Equatoria State, South Sudan, received three to five rounds of mass drug administration with antibiotics.

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Trachoma recrudescence is a serious concern for trachoma control programs. Programs define recrudescence as the return of trachomatous inflammation-follicular (TF) prevalence above elimination threshold (≥5%) on district-level trachoma surveillance surveys (TSSs). This study aimed to determine potential correlates of trachoma recrudescence within a historically highly endemic region.

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Objective: Loss of sense of smell is a cardinal symptom of chronic rhinosinusitis with nasal polyps (CRSwNP) and significantly impacts health-related quality-of-life. Dupilumab significantly improved smell outcomes (loss of smell [LoS] score; University of Pennsylvania Smell Identification Test [UPSIT]) versus placebo in the phase 3 SINUS-24/-52 studies (clinicaltrials.gov, NCT02898454/NCT02912468) in patients with severe CRSwNP.

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IL-4 and IL-13 have non-redundant effects in olfaction, with loss of smell in mice evoked only by intranasal administration of IL-4, but not IL-13. IL-4-evoked pathophysiological effects on olfaction is independent of compromised structural integrity of the olfactory neuroepithelium. IL-4-IL-4Rα signaling modulates neuronal crosstalk with immune cells, suggesting a functional link between olfactory impairment and neuroinflammation.

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Article Synopsis
  • Trachoma is aimed for global elimination by 2030, with a focus on using IgG antibody measurements in children for monitoring and decision-making in public health programs.
  • There are no existing guidelines for using serology in trachoma control, highlighting a larger issue in the field of disease elimination and epidemiology.
  • Researchers analyzed IgG levels in 63,911 children from various regions to determine seroconversion rates and proposed a method to assess when population transmission falls below or exceeds intervention thresholds, aiding trachoma program strategies.
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  • * It’s important for doctors to recognize this problem because it can show how serious the CRS is and how well treatment is working.
  • * There are medicines and treatments like nasal sprays and surgery that can help improve smell, and new treatments are being researched too.
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The purpose of this study was to investigate the correlation between bacterial load of Chlamydia trachomatis as measured from quantitative polymerase chain reaction (qPCR) and the relative clinical severity of trachomatous inflammation. Individuals with trachoma from rural communities in Ethiopia had photographs taken as well as swabs obtained of the upper tarsal conjunctivas. Conjunctival swabs were processed with PCR assay, which provided quantitative results of ocular chlamydial load.

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Background: Frequently reported outcomes of clinical trials in chronic rhinosinusitis with nasal polyps (CRSwNP) may have limited relatability for patients.

Objective: To enhance the patient relatability of outcomes in dupilumab clinical trials for CRSwNP, daily symptom scores were used to determine new patient‑centered end points: mild-to-no-symptom months (MSM) and symptom-free months (SFM).

Methods: This work is a post hoc analysis of patients receiving dupilumab 300 mg or placebo every 2 weeks for 24 weeks (SINUS-24 study; NCT02912468) or 52 weeks (SINUS‑52; NCT02898454).

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Background: Dupilumab and mepolizumab have shown efficacy and safety in treating chronic rhinosinusitis with nasal polyps (CRSwNP).

Objective: Without available results from head-to-head randomized control trials (RCTs) comparing dupilumab with other biologics, we conducted an indirect treatment comparison (ITC) with mepolizumab.

Methods: A systematic literature review identified RCTs of biologics in CRSwNP.

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Purpose: Trachoma surveys are used to estimate the prevalence of trachomatous inflammation-follicular (TF) to guide mass antibiotic distribution. These surveys currently rely on human graders, introducing a significant resource burden and potential for human error. This study describes the development and evaluation of machine learning models intended to reduce cost and improve reliability of these surveys.

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Objective: To evaluate the association between smell loss and other aspects of disease, and evaluate dupilumab efficacy in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate or severe smell loss.

Methods: This post-hoc analysis of the SINUS-24/52 studies (NCT02912468/NCT02898454) analyzed nasal polyp score (NPS, 0-8), nasal congestion/obstruction (NC, 0-3), Lund-Mackay CT-scan score (LMK-CT, 0-24), rhinosinusitis severity visual analog scale (RS-VAS, 0-10), and 22-item Sinonasal Outcome Test (SNOT-22, 0-110) according to baseline monthly average patient-reported loss of smell scores (LoS, 0-3) of >1 to 2 (moderate) or >2 to 3 (severe) in patients randomized to dupilumab 300 mg or placebo every 2 weeks.

Results: Of 724 patients randomized, baseline LoS was severe in 601 (83%) and moderate in 106 (15%).

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Background: Responder analyses of SINUS phase 3 study data have shown clinically meaningful improvements across multiple outcomes of treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) with dupilumab.

Objective: Our aim was to gain a better understanding of dynamics of the response to dupilumab over 52 weeks.

Methods: We used data from the SINUS-52 (ClinicalTrials.

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Objectives: A 6-week course of tetracycline eye ointment is an alternative to single -dose oral azithromycin in annual mass drug administration for trachoma control. Compliance with the recommended tetracycline eye ointment regimen has not been well characterised when administered as part of a trachoma control program.

Methods: A routine mass drug administration for trachoma was carried out in 40 communities in the Amhara region of Ethiopia.

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Community-wide distribution of azithromycin, otherwise known as mass drug administration (MDA), is a component of the World Health Organization-endorsed SAFE strategy for the elimination of trachoma as a public health problem. In the Republic of South Sudan, 2.9 million people are known to live in areas that are known to require interventions and warrant MDA.

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Background: Promotion of facial cleanliness is recommended for the elimination of blinding trachoma, largely because of observational studies that have found an association between various measures of facial uncleanliness and trachoma. However, when a field grader assesses both facial cleanliness and trachoma, associations may be biased. Assessment of photographs of the face and conjunctiva by masked graders may provide a less biased estimate of the relationship between facial cleanliness and trachoma.

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Article Synopsis
  • Persistent trachoma is a significant public health issue, especially in Ethiopia, where it is defined as having a TF prevalence of ≥5% in children after multiple impact surveys.
  • A 2019 study investigated the epidemiology of Chlamydia trachomatis infection, the cause of trachoma, across seven districts with persistent cases, revealing TF prevalence between 11.8% and 36.1%.
  • Findings indicated a strong correlation between infection and households lacking latrines, suggesting that intensified intervention strategies over the next 3-5 years are essential to meet the global trachoma elimination goal by 2030.
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  • Sudan has multiple neglected tropical diseases, with a study conducted in North Darfur sampling 8,322 individuals from 3 localities to assess trachoma and other diseases.
  • The serosurvey found very low rates of antibodies for onchocerciasis and variable rates for lymphatic filariasis, indicating some exposure but a need for further investigation.
  • High schistosomiasis antibody levels among school-aged children suggest a need for additional mapping and treatment planning, although the study faced challenges due to the lack of established gold standards for interpreting results.
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  • Trachomatous scarring progresses independently of active Chlamydia trachomatis infections, suggesting other factors contribute to scarring beyond ongoing transmission.
  • A study in Amhara, Ethiopia assessed 729 adults for scarring severity using a photographic scale, revealing severe scarring (S4) was most prevalent among older individuals (32.6% in ages 60+) compared to younger adults (6.2% in ages 15-19).
  • Key risk factors for increased scarring severity included being female, older age, and higher district-level prevalence of trachomatous follicular inflammation, indicating a need for continued surveillance even after achieving trachoma elimination targets.
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Objectives: This analysis assessed disease characteristics and response to dupilumab treatment in male and female patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) (SINUS-52 study; NCT02898454).

Methods: Patients received dupilumab 300 mg or placebo every 2 weeks for 52 weeks on background intranasal corticosteroids. Efficacy was assessed through Week 52 using nasal polyp score (NPS), nasal congestion/obstruction score, loss of smell score and University of Pennsylvania Smell Identification Test score.

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The SAFE (Surgery, Antibiotics, Facial cleanliness, Environmental improvement) strategy is the WHO's endorsed approach for eliminating trachoma as a public health problem; however, not all components have been treated equally. Historically, the F and E components have not been prioritized owing to their perceived complexity. With school enrollment increasing in Ethiopia, development of a national school health program that is focused on the F and E components represents an opportunity to strengthen the SAFE strategy in the country.

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Chronic rhinosinusitis with nasal polyps (CRSwNP) is predominantly a type 2 inflammatory disease associated with type 2 (T2) cell responses and epithelial barrier, mucociliary, and olfactory dysfunction. The inflammatory cytokines interleukin (IL)-4, IL-13, and IL-5 are key mediators driving and perpetuating type 2 inflammation. The inflammatory responses driven by these cytokines include the recruitment and activation of eosinophils, basophils, mast cells, goblet cells, M2 macrophages, and B cells.

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Trachoma is the leading infectious cause of blindness worldwide and is now largely confined to around 40 low- and middle-income countries. It is caused by Chlamydia trachomatis (Ct), a contagious intracellular bacterium. The World Health Organization recommends mass drug administration (MDA) with azithromycin for treatment and control of ocular Ct infections, alongside improving facial cleanliness and environmental conditions to reduce transmission.

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Article Synopsis
  • The Sudan Federal Ministry of Health conducted trachoma prevalence surveys in three districts of North Darfur from 2019-2020 to assess the disease's impact on children aged 1-9 years, particularly in areas that had not previously received mass drug administration (MDA).
  • Over 6,000 individuals were examined, and the results showed endemic levels of trachomatous inflammation-follicular (TF) in two localities, with TF rates of 15.6% and 11.0% while the third locality reported a much lower rate of 1.4%.
  • Serological tests indicated a long history of exposure to Chlamydia trachomatis, highlighting the need for MDA in
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Background: Trachoma recrudescence after elimination as a public health problem has been reached is a concern for control programs globally. Programs typically conduct district-level trachoma surveillance surveys (TSS) ≥ 2 years after the elimination threshold is achieved to determine whether the prevalence of trachomatous inflammation-follicular (TF) among children ages 1 to 9 years remains <5%. Many TSS are resulting in a TF prevalence ≥5%.

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