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Background There has been a successful push towards parasitological diagnosis of malaria in Africa, mainly with rapid diagnostic tests (mRDTs), which has reduced over-prescribing of artemisinin-based combination therapies (ACT) to malaria test-negative patients. The effect on prescribing for test-positive patients has received much less attention. Malaria infection in endemic Africa is often most dangerous for young children and those in low-transmission settings. This study examined non-prescription of antimalarials for patients with malaria infection demonstrated by positive mRDT results, and in particular these groups who are most vulnerable to poor outcomes if antimalarials are not given. Methods Analysis of data from 562,762 patients in 8 studies co-designed as part of the ACT Consortium, conducted 2007–2013 in children and adults, in Cameroon, Ghana, Nigeria, Tanzania, and Uganda, in a variety of public and private health care sector settings, and across a range of malaria endemic zones. Results Of 106,039 patients with positive mRDT results (median age 6 years), 7426 (7.0%) were not prescribed an ACT antimalarial. The proportion of mRDT-positive patients not prescribed ACT ranged across sites from 1.3 to 37.1%. For patients under age 5 years, 3473/44,539 (7.8%) were not prescribed an ACT, compared with 3833/60,043 (6.4%) of those aged ≥ 5 years. The proportion of Conclusions In eight studies of mRDT implementation in five African countries, substantial proportions of patients testing mRDT-positive were not prescribed an ACT antimalarial, and many were not prescribed an antimalarial at all. Patients most vulnerable to serious outcomes, children Trial registration Reported in individual primary studies.

We propose a framework for the understanding of the pathophysiology and management of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) that considers wider determinants of health and long-term temporal variation in pathophysiological features and disease phenotype throughout the natural history of the disease. As in other chronic diseases, ME/CFS evolves through different stages, from asymptomatic predisposition, progressing to a prodromal stage, and then to symptomatic disease. Disease incidence depends on genetic makeup and environment factors, the exposure to an insult, or repeated insults, and the nature of the host response. In people who develop ME/CFS, normal homeostatic processes in response to adverse insults may be replaced by aberrant responses leading to dysfunctional states. Thus, the predominantly neuro-immune and autonomic manifestations, underlined by a hyper-metabolic state, that characterise early disease, may be followed by various processes leading to multi-systemic related symptoms. This abnormal metabolic state and the effects of a range of mediators such as products of oxidative and nitrosamine stress, may lead to progressive cell and metabolic dysfunction culminating in a hypometabolic state with low energy production. These processes do not seem to happen uniformly; although a spiralling of progressive inter-related and self-sustaining abnormalities may ensue, reversion to states of milder abnormalities is possible if the host is able to restate responses to improve homeostatic equilibrium. Disease management and research efforts should seek to identify and apply strategies targeted at the different pathophysiological dysfunctions that characterise different disease stages. As disease presentation varies over time, no single case description, set of diagnostic criteria, or molecular feature is currently diagnostic for all patients at all times. While acknowledging its limitations due to the incomplete research evidence, we suggest the proposed framework may improve research design and health care interventions for people with ME/CFS.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling disease characterized by unexplained incapacitating fatigue, accompanied by variable multi-systemic symptoms. ME/CFS causes a significant personal and public health burden, and urgently requires the coordination of research efforts to investigate its etiology and pathophysiology and to develop and validate sensitive and specific biomarkers to confirm diagnosis. This narrative paper describes how people with ME/CFS, together with a multidisciplinary team of researchers, have established the UK ME/CFS Biobank (UKMEB), a unique research infrastructure specifically designed to expedite biomedical research into ME/CFS. We describe the journey that led to its conceptualization and operation, and how the resource has served as a model disease-specific biobank, aggregating human biospecimens alongside comprehensive health information on participants. The UKMEB currently has data and samples from 600 donors including people with ME/CFS and a comparison group with multiple sclerosis and healthy controls. A longitudinal sub-cohort has been established of participants having follow-up assessments at multiple time-points. As an open resource for quality and ethical research into ME/CFS, biological samples and data have not only been analyzed within our research team but have also been shared with researchers across Europe, America and the Middle East. We continue to encourage researchers from academic and commercial sectors to access the UKMEB. Major steps have been taken and challenges remain; these include sustainability and expansion, and harmonization of processes to facilitate integration with other bioresources and databanks internationally.