Drug-Drug Interactions of Infectious Disease Treatments in Low-Income Countries: A Neglected Topic?

Despite recent advances in recognizing and reducing the risk of drug-drug interactions (DDIs) in developed countries, there are still significant challenges in managing DDIs in low-income countries (LICs) worldwide. In the treatment of major infectious diseases in these regions, multiple factors contribute to ineffective management of DDIs that lead to loss of efficacy or increased risk of adverse events to patients. Some of these difficulties, however, can be overcome. This review aims to evaluate the inherent complexities of DDI management in LICs from pharmacological standpoints and illustrate the unique barriers to effective management of DDIs, such as the challenges of co-infection and treatment settings. A better understanding of comprehensive drug-related properties, population-specific attributes, such as physiological changes associated with infectious diseases, and the use of modeling and simulation techniques are discussed, as they can facilitate the implementation of optimal treatments for infectious diseases at the individual patient level.

Repurposing Drugs Based on Evolutionary Relationships Between Targets of Approved Drugs and Proteins of Interest.

Drug repurposing has garnered much interest as an effective method for drug development among biopharmaceutical companies. The availability of information on complete sequences of genomes and their associated biological data, genotype-phenotype-disease relationships, and properties of small molecules offers opportunities to explore the repurpose-able potential of existing pharmacopoeia. This method gains further importance, especially, in the context of development of drugs against infectious diseases, some of which pose serious complications due to emergence of drug-resistant pathogens. In this article, we describe computational means to achieve potential repurpose-able drug candidates that may be used against infectious diseases by exploring evolutionary relationships between established targets of FDA-approved drugs and proteins of pathogen of interest.

Innovative Approaches to Improve Anti-Infective Vaccine Efficacy.

Safe and efficacious vaccines are arguably the most successful medical interventions of all time. Yet the ongoing discovery of new pathogens, along with emergence of antibiotic-resistant pathogens and a burgeoning population at risk of such infections, imposes unprecedented public health challenges. To meet these challenges, innovative strategies to discover and develop new or improved anti-infective vaccines are necessary. These approaches must intersect the most meaningful insights into protective immunity and advanced technologies with capabilities to deliver immunogens for optimal immune protection. This goal is considered through several recent advances in host-pathogen relationships, conceptual strides in vaccinology, and emerging technologies. Given a clear and growing risk of pandemic disease should the threat of infection go unmet, developing vaccines that optimize protective immunity against high-priority and antibiotic-resistant pathogens represents an urgent and unifying imperative.

The timing of introduction of complementary foods and later health.

Complementary food is needed when human milk (or infant formula) alone is no longer sufficient for nutritional reasons. The timing of introduction needs to be determined on an individual basis although 6 months of exclusive breastfeeding can be recommended for most healthy term infants. Solid foods are intended to 'complement' ongoing breastfeeding with those dietary items whose intake has become marginal or insufficient. Both breastfeeding and complementary feeding can have direct or later consequences on health. Possible short-term health effects concern growth velocity and infections while possible long-term effects may relate to obesity, cardiovascular disease, autoimmunity (celiac disease and type 1 diabetes) and atopic disorders. For most of these it is impossible on the basis of the available evidence to conclude on the age when risks related to the start of complementary feeding are lowest or highest, with the possible exception of infections and early growth velocity. For undesirable health consequences, whilst potential mechanisms are recognized, the evidence from mostly observational studies is insufficient and requires more and prospective research. While the 6-month goal is desirable, introduction of suitable complementary food after 4 completed months with ongoing breastfeeding can be considered without adverse health consequences for infants living in affluent countries. Even less evidence on the consequences of the timing of complementary food introduction is available for formula-fed infants.

Energy cost of infection burden: an approach to understanding the dynamics of host-pathogen interactions.

A mathematical model of long-term immune defense against infection was used to estimate the energy involved in the principal processes of immune resistance during periods of health and infection. From these values, an optimal level of energy was determined for immune response depending on infection burden. The present findings suggest that weak but prevalent pathogens lead to latent or chronic infection, whereas more virulent but less prevalent pathogens result in acute infection. This energy-based approach offers insight into the mechanisms of immune system adaptation leading to the development of chronic infectious diseases and immune deficiencies.