Summary Patient adherence is a major determinant of the therapeutic response to antimalarial drugs, as most treatments are taken at home without medical supervision. With the introduction of new, effective, but more expensive antimalarials, there is concern that the high levels of efficacy observed in clinical trials may not be translated into effectiveness in the normal context of use. We reviewed available published evidence on adherence to antimalarial drugs and community drug usage; 24 studies were identified of which nine were ‘intervention’ studies, seven were classified as ‘outcome studies’, and the remainder were purely descriptive studies of antimalarial adherence. Definitions, methods, and results varied widely. Adherence was generally better when treatments were effective, and was improved by interventions focusing on provider knowledge and behaviour, packaging, and provision of correct dosages. There is insufficient information on this important subject, and current data certainly do not justify extrapolation from results with ineffective drugs to new effective treatments. Research in this area would benefit from of standardization of methodologies and the application of pharmacokinetic modelling.
Two hundred years after Singapore's foundation by Stamford Raffles in 1819, this book reflects on the historical development of the city, putting forward much new research and new thinking. It discusses Singapore's emergence as a regional economic hub, explores its strategic importance and considers its place in the development of the British Empire. Subjects covered include the city's initial role as a strategic centre to limit the resurgence of Dutch power in Southeast Asia after the Napoleonic Wars, the impact of the Japanese occupation and the reasons for Singapore's exit from the Malaysian Federation in 1965.
No abstract is provided for this article.
No abstract is provided for this article.
In many large animals, changes in fighting ability within breeding seasons or across the lifetime of individuals are related to changes in body condition but not to obvious changes in size. In situations where a conflict of interests is likely to lead to a fight, we might consequently expect opponents to assess each other on traits which are related to variation in body condition. This appears to be the case among red deer stags. Competing
Parasite clearance rates are important measures of anti-malarial drug efficacy. They are particularly important in the assessment of artemisinin resistance. The slope of the log-linear segment in the middle of the parasite clearance curve has the least inter-individual variance and is the focus of therapeutic assessment. The factors affecting parasite clearance are reviewed. Methods of presentation and the approaches to analysis are discussed.
Plasmodium vivax is a major cause of febrile illness in endemic areas of Asia, Central and South America, and the horn of Africa. P. vivax infections are characterized by relapses of malaria arising from persistent liver stages of the parasite (hypnozoites), which can be prevented currently only by 8-aminoquinoline anti-malarials. Tropical P. vivax infections relapse at approximately 3-week intervals if rapidly eliminated anti-malarials are given for treatment, whereas in temperate regions and parts of the sub-tropics, P. vivax infections are characterized by either a long incubation or a long-latency period between illness and relapse – in both cases approximating 8–10 months. The epidemiology of the different relapse phenotypes has not been defined adequately despite obvious relevance to malaria therapeutic assessment, control, and elimination. The number of sporozoites inoculated by the anopheline mosquito is an important determinant of both the timing and the number of relapses. The intervals between P. vivax relapses display a remarkable periodicity which has not been explained. Evidence is presented that the proportion of patients who have successive relapses is relatively constant and that the factor which activates hypnozoites and leads to regular interval relapse in vivax malaria is the systemic febrile illness itself. It is proposed that in endemic areas, a large proportion of the population harbours latent hypnozoites which can be activated by a systemic illness such as vivax or falciparum malaria. This explains the high rates of vivax following falciparum malaria, the high proportion of heterologous genotypes in relapses, the higher rates of relapse in people living in endemic areas compared with artificial infection studies, and, by facilitating recombination between different genotypes, contributes to P. vivax genetic diversity particularly in low transmission settings. Long-latency P. vivax phenotypes may be more widespread and more prevalent than currently thought. These observations have important implications for the assessment of radical treatment efficacy and for malaria control and elimination.
Antimalarial drug efficacy in uncomplicated malaria should be assessed parasitologically in large, community-based trials, enrolling the age groups most affected by clinical disease. For rapidly eliminated drugs, a 28-day follow-up is needed, but, for slowly eliminated drugs, up to nine weeks could be required to document all recrudescences, and, when possible, the drug levels should also be measured. The WHO 14-day assessments are neither sensitive nor specific. In tropical Plasmodium vivax and Plasmodium ovale infections treated with chloroquine, the first relapse is usually suppressed by residual drug levels. A relapse cannot be distinguished confidently from a recrudescence. Host immunity is a major contributor to the therapeutic response, and can make failing drugs appear effective.
No abstract is provided for this article.
In many social vertebrates, variation in group persistence exerts an important effect on individual fitness and population demography. However, few studies have been able to investigate the failure of groups or the causes of the variation in their longevity. We use data from a long‐term study of cooperatively breeding meerkats, Suricata suricatta , to investigate the different causes of group failure and the factors that drive these processes. Many newly formed groups failed within a year of formation, and smaller groups were more likely to fail. Groups that bred successfully and increased their size could persist for several years, even decades. Long‐lived groups principally failed in association with the development of clinical tuberculosis, Mycobacterium suricattae , a disease that can spread throughout the group and be fatal for group members. Clinical tuberculosis was more likely to occur in groups that had smaller group sizes and that had experienced immigration.
