Assessment of the Current Surveillance System for Human Leptospirosis in Ecuador by Decision Analytic Modeling.

Leptospirosis is a globally disseminated zoonotic disease with no national surveillance systems. On the other hand, surveillance is crucial for improving population health, and surveillance systems produce data that motivates action. Unfortunately, like many other countries, Ecuador put in place a monitoring system that has never been tested. The goal of this study was to use scenario tree modeling to assess the sensitivity of Ecuador's current national surveillance system to human leptospirosis as the basis for an economic assessment of the system. We created a decision-tree model to analyze the current system's sensitivity. The inputs were described as probabilities distributions, and the model assessed the program's sensitivity as an output. The model also considers the geographical and weather variations across Ecuador's three continental regions: Andean, Amazonia, and the Coast. Several data sources were used to create the model, including leptospirosis records from Ecuador's Ministry of Public Health, national and international literature, and expert elicitation, all of which were incorporated in a Bayesian framework. We were able to determine the most critical parameters influencing each scenario's output (CSU) sensitivity through sensitivity analysis. The Coast region had the best sensitivity scenario, with a median of 0.85% (IC 95% 0.41-0.99), followed by the Amazonia with a median of 0.54% (CI 95% 0.18-0.99) and the Andes with a median of 0.29% (CI 95% 0.02-0.89). As per the sensitivity study, the most influential criteria on the system's sensitivity were "Attendance or probability of going to a health center" and "probability of having symptoms," notably for the Coast and Amazonia Regions.

Mechanochemical Synthesis of A Novel Eutectic of the Antimicrobial Nitazoxanide with Improved Dissolution Performance

Background: Nitazoxanide (NTZ) is a broad spectrum antimicrobial agent with poor aqueous solubility and low bioavailability. [...]the generation of new solid forms of NTZ is relevant to improve its unfavorable properties. Methods: NTZ-SAC mixtures were prepared by neat and liquid-assisted grinding (LAG) and characterized using differential scanning calorimetry (DSC), hot stage microscopy (HSM), X-ray Powder Diffraction (XRPD), 13C Solid-state Nuclear Magnetic Resonance (SSNMR) and Diffuse Reflectance Infrared Fourier Transform (DRIFT) spectroscopy. Introduction Nitazoxanide [2-(acetyloxy)-N-(5-nitro-2-thiazolyl) benzamide, NTZ] (Figure 1) is a nitrothiazole derivative used in the treatment of diarrhea caused by Cryptosporidium parvum and Giardia intestinalis in adults and children at least 12 months of age.1 NTZ is also active against numerous other parasitic pathogens and viruses, including Trypanosoma cruzi (the causative agent of American trypanosomiasis),2 Leishmania mexicana,2 the ulcer-causing pathogen Helicobacter pylori,3 multidrug resistant strains of Mycobacterium tuberculosis,1 as well as respiratory viruses, rotavirus, norovirus, coronavirus, hepatitis B and C, dengue-2, yellow fever, Japanese encephalitis, and human immunodeficiency viruses.4 Moreover, NTZ has shown anticancer activity,4 and is a promising compound for the treatment of neuropathic pain,4 the Ebola virus disease4 and is also under investigation for potential use in COVID-19 treatment.5 Although NTZ is an agent with diverse pharmacological activities and minimal toxicity, it has unfavorable physicochemical and biopharmaceutical properties, in particular very poor aqueous solubility6 and low bioavailability,4 and this provided the motivation for discovering new solid forms which may improve its solubility, dissolution rate, and bioavailability, and thus provide improved therapeutic options for patients. [...]NTZ has been in the focus of pharmaceutical research to discover and prepare alternative solid forms such as cyclodextrin complexes,7,8 solid dispersions,9 cocrystals10 and cocrystal alloys.11 Regarding NTZ cocrystals, it was found that it cocrystallized with five organic acids [succinic acid,10 glutaric acid,10 2,5-dihydroxybenzoic acid,10 p-aminobenzoic acid and p-aminosalicylic acid11], showing a common heterodimeric synthon formed between the carboxyl group of the acid coformer and the carboxamidine group of NTZ (Figure 1), namely the carboxyl-carboxamidine synthon.10,11 Pursuing our interest in discovering new solid forms of NTZ, the aim of this study was to determine if NTZ can be partnered with a non-carboxylic acid coformer such as saccharine (SAC, pKa = 2.212, Figure 1) which cannot form the above-mentioned carboxyl-carboxamidine synthon with NTZ, but is able to generate N-H···O, S=O··H-N, O-H-O and N-H-N hydrogen bonds with drugs possessing OH, NH or carbonyl groups12,13 such as NTZ, leading to cocrystals, salts or eutectics, with the last representing a whole new paradigm of noncovalent derivatives14 and technology at par with other crystal engineering techniques in improving clinically significant attributes of a drug14 such as solubility, stability, and bioavailability, as demonstrated for curcurmin,15 hesperetin,14 and leflunomide.16 In effect, depending upon various factors, during cocrystallization, an amalgamation of two complementary interacting materials lead to the formation of a specific product which can be any of the multicomponent organic adduct (solvate, molecular salt, eutectic or a cocrystal).16 The formation of either cocrystal or eutectic during cocrystallization is mutually exclusive and a win-win situation.16 According to Cherukuvada and Nangia,17 the materials with strong adhesive (hetero) interactions between the unlike components will lead to cocrystals whereas those having stronger cohesive (homo/self) interactions will more often give rise to solid solutions (for similar structures of components) and eutectics (for different structures of components).