Toward health system strengthening in low- and middle-income countries: insights from mathematical modeling of drug supply chains.

BACKGROUND: Global health priority setting increasingly focuses on understanding the functioning of health systems and on how they can be strengthened. Beyond vertical programs, health systems research should examine system-wide delivery platforms (e.g. health facilities) and operational elements (e.g. supply chains) as primary units of study and evaluation. METHODS: We use dynamical system methods to develop a simple analytical model for the supply chain of a low-income country's health system. In doing so, we emphasize the dynamic links that integrate the supply chain within other elements of the health system; and we examine how the evolution over time of such connections would affect drug delivery, following the implementation of selected interventions (e.g. enhancing road networks, expanding workforce). We also test feedback loops and forecasts to study the potential impact of setting up a digital system for tracking drug delivery to prevent drug stockout and expiration. RESULTS: Numerical simulations that capture a range of supply chain scenarios demonstrate the impact of different health system strengthening interventions on drug stock levels within health facilities. Our mathematical modeling also points to how implementing a digital drug tracking system could help anticipate and prevent drug stockout and expiration. CONCLUSION: Our mathematical model of drug supply chain delivery represents an important component toward the development of comprehensive quantitative frameworks that aim at describing health systems as complex dynamical systems. Such models can help predict how investments in system-wide interventions, like strengthening drug supply chains in low-income settings, may improve population health outcomes.

Milk Fat Globules Hamper Adhesion of Enterohemorrhagic Escherichia coli to Enterocytes: In Vitro and in Vivo Evidence.

Enterohemorrhagic Escherichia coli (EHEC; E. coli) are food-borne agents associated with gastroenteritis, enterocolitis, bloody diarrhea and the hemolytic-uremic syndrome (HUS). Bovine milk glycans have been shown to contain oligosaccharides which are similar to host epithelial cell receptors and can therefore prevent bacterial adhesion. This study aimed to describe interactions between EHEC O157:H7 EDL933 and O26:H11 21765 and milk fat globules (MFGs) in raw milk and raw milk cheese, and the impact of MFGs on EHEC strains adhesion to the intestinal tract in vitro and in vivo. Both EHEC serotypes clearly associated with native bovine MFGs and significantly limited their adhesion to a co-culture of intestinal cells. The presence of MFGs in raw milk cheese had two effects on the adhesion of both EHEC serotypes to the intestinal tracts of streptomycin-treated mice. First, it delayed and reduced EHEC excretion in mouse feces for both strains. Second, the prime implantation site for both EHEC strains was 6 cm more proximal in the intestinal tracts of mice fed with contaminated cheese containing less than 5% of fat than in those fed with contaminated cheese containing 40% of fat. Feeding mice with 40% fat cheese reduced the intestinal surface contaminated with EHEC and may therefore decrease severity of illness.