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The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world. Similarities with climate change are evident. Many efforts have been made to describe the many different facets of antibiotic resistance and the interventions needed to meet the challenge. However, coordinated action is largely absent, especially at the political level, both nationally and internationally. Antibiotics paved the way for unprecedented medical and societal developments, and are today indispensible in all health systems. Achievements in modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, which we today take for granted, would not be possible without access to effective treatment for bacterial infections. Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions are immediately taken. Here, we describe the global situation of antibiotic resistance, its major causes and consequences, and identify key areas in which action is urgently needed., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Rift Valley fever (RVF) is an emerging arthropod-borne zoonoses of global agricultural and public health importance. In December 2006, an RVF outbreak was recognized in Kenya which led to the deployment of international response laboratory teams to the area., Objectives: A field laboratory was operated in Malindi, Kenya to provide safe sample handling and molecular testing for RVF virus (RVFV) as well as selected other pathogens for differential diagnosis., Study Design: Safe sample handling was carried out using a negative pressure flexible film isolator (glovebox) and commercial reagents to inactivate clinical specimens and purify nucleic acid. Whole blood was routinely used for diagnostic testing although paired plasma samples were also tested in select cases. Subsequently, human macrophages were tested in vitro for their susceptibility to RVFV., Results: The field laboratory received samples from 33 individuals and a definite laboratory diagnosis was provided in 16 of these cases. Using molecular diagnostic techniques, RVFV was more consistently detected in whole blood than in plasma samples most likely due to association of RVFV with blood cells. Subsequent in vitro studies identified macrophages as a target cell for RVFV replication., Conclusions: RVFV appears to replicate in blood cells such as macrophages. Thus, the sensitivity of molecular diagnostic testing is improved if whole blood is used as the clinical specimen rather than plasma or serum., (Published by Elsevier B.V.)

The growing threat from resistant organisms calls for concerted action to prevent the emergence of new resistant strains and the spread of existing ones. Developing countries have experienced unfavourable trends in resistance-as detailed in part I, published last month--and implementation of many of the containment strategies recommended by WHO is complicated by universal, as well as developing country-specific, factors. The control of selective pressure for resistance could potentially be addressed through educational and other interventions for orthodox and unorthodox prescribers, distributors, and consumers of antimicrobials. At national levels, the implementation of drug use strategies--eg, combination therapy or cycling--may prove useful to lengthen the lifespan of existing and future agents. Programmes such as the Integrated Management of Childhood Illnesses (IMCI) and directly observed short-course therapy (DOTS) for tuberculosis are prescriber-focused and patient-focused, respectively, and have both been shown to positively influence factors that contribute to the selective pressure that affects resistance. The institution of interventions to prevent the transmission of infectious diseases could also lead to beneficial effects on the prevalence of resistance, as has vaccination against Haemophilus influenzae type B and Streptococcus pneumoniae. There has been an upsurge in the number of organisations and programmes that directly address issues of resistance, and collaboration could be one way to stem the dire trend. Additional factors such as unregulated drug availability, inadequate antimicrobial drug quality assurance, inadequate surveillance, and cultures of antimicrobial abuse must be addressed to permit a holistic strategy for resistance control.

The global problem of antimicrobial resistance is particularly pressing in developing countries, where the infectious disease burden is high and cost constraints prevent the widespread application of newer, more expensive agents. Gastrointestinal, respiratory, sexually transmitted, and nosocomial infections are leading causes of disease and death in the developing world, and management of all these conditions has been critically compromised by the appearance and rapid spread of resistance. In this first part of the review, we have summarised the present state of resistance in these infections from the available data. Even though surveillance of resistance in many developing countries is suboptimal, the general picture is one of accelerating rates of resistance spurred by antimicrobial misuse and shortfalls in infection control and public health. Reservoirs for resistance may be present in healthy human and animal populations. Considerable economic and health burdens emanate from bacterial resistance, and research is needed to accurately quantify the problem and propose and evaluate practicable solutions. In part II, to be published next month, we will review potential containment strategies that could address this burgeoning problem.