5 research outputs found
Molecular Imaging of Pulmonary Tuberculosis in an Ex-Vivo Mouse Model Using Spectral Photon-Counting Computed Tomography and Micro-CT
Assessment of disease burden and drug efficacy is achieved preclinically using high resolution micro computed tomography (CT). However, micro-CT is not applicable to clinical human imaging due to operating at high dose. In addition, the technology differences between micro-CT and standard clinical CT prevent direct translation of preclinical applications. The current proof-of-concept study presents spectral photon-counting CT as a clinically translatable, molecular imaging tool by assessing contrast uptake in an ex-vivo mouse model of pulmonary tuberculosis (TB). Iodine, a common contrast used in clinical CT imaging, was introduced into a murine model of TB. The excised mouse lungs were imaged using a standard micro-CT subsystem (SuperArgus) and the contrast enhanced TB lesions quantified. The same lungs were imaged using a spectral photoncounting CT system (MARS small-bore scanner). Iodine and soft tissues (water and lipid) were materially separated, and iodine uptake quantified. The volume of the TB infection quantified by spectral CT and micro-CT was found to be 2.96 mm(3) and 2.83 mm(3), respectively. This proof-of-concept study showed that spectral photon-counting CT could be used as a predictive preclinical imaging tool for the purpose of facilitating drug discovery and development. Also, as this imaging modality is available for human trials, all applications are translatable to human imaging. In conclusion, spectral photon-counting CT could accelerate a deeper understanding of infectious lung diseases using targeted pharmaceuticals and intrinsic markers, and ultimately improve the efficacy of therapies by measuring drug delivery and response to treatment in animal models and later in humans
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Village-integrated eye workers for prevention of corneal ulcers in Nepal (VIEW study): a cluster-randomised controlled trial
BackgroundCorneal ulcers are a common cause of blindness in low-income and middle-income countries, usually resulting from traumatic corneal abrasions during agricultural work. Antimicrobial prophylaxis of corneal abrasions can help prevent corneal ulcers, but delays in the initiation of therapy are frequent. We aimed to assess whether a community-based programme for corneal ulcer prevention would reduce the incidence of corneal ulceration.MethodsA cluster-randomised trial was performed in village development committees (VDCs) in Nepal. VDCs in the catchment area of Bharatpur Eye Hospital, Nepal with less than 15 000 people were eligible for inclusion. We randomly assigned (1:1) VDCs to either an intervention group or a control group. In the intervention VDCs, existing female community health volunteers (FCHVs) were trained to diagnose corneal abrasions and provide a 3-day course of ophthalmic antimicrobials to their patients. In the control VDCs, FCHVs did not provide this intervention. Participants were not masked given the nature of the intervention. Both groups were followed up for 3 years for photographic evidence of corneal ulceration. The primary outcome was the incidence of corneal ulceration, determined by masked assessment of corneal photographs. The analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT01969786.FindingsWe assessed 112 VDCs, of which 24 were enrolled. The study was performed between Feb 4, 2014, and Oct 20, 2017. 12 VDCs were randomly assigned to the intervention group and 12 to the control group. 252 539 individuals were included in the study (130 579 in the intervention group and 121 960 in the control group). FCHVs diagnosed and provided antimicrobials for 4777 corneal abrasions. The census identified 289 corneal ulcers among 246 893 person-years in the intervention group (incidence 1·21 cases [95% CI 0·85-1·74] per 1000 person-years) and 262 corneal ulcers among 239 170 person-years in the control group (incidence 1·18 cases [0·82-1·70] per 1000 person-years; incidence rate ratio 1·03 [95% CI 0·63-1·67]; p=0·93). Medication allergy was self-reported in 0·2% of participants.InterpretationWe did not detect a reduction in the incidence of corneal ulceration during the first 3 years of a community-based corneal ulcer prevention programme. Further study might be warranted in more rural areas where basic eye care facilities are not available.FundingNational Eye Institute