Artemisinin resistance in Plasmodium falciparum has emerged in South East Asia. Evidence of resistance in Western Cambodia was documented over six years ago, and last year clear evidence of resistance was reported on the Thailand- Myanmar border. As artemisinin derivatives are the cornerstone of antimalarial treatment both for uncomplicated and severe malaria, their loss will increase morbidity and mortality, and could derail current containment and elimination efforts. In the treatment of severe falciparum malaria artesunate reduced mortality by approximately one third compared with quinine. This resulted from greater parasiticidal activity against circulating ring stage parasites, the very property that is lost in artemisinin-resistance. If we have to return to quinine for the treatment of severe malaria, mortality will rise again. In the treatment of uncomplicated malaria artemisinin resistance results in slower parasite clearance and consequently slower therapeutic responses. Times to recovery are slower, treatment failure rates higher, and transmissibility of the treated infection greater. The reduced antiparasitic effect means that the partner drug now has toeliminate a greater proportion of the infecting parasite biomass, and so there is a greater probability of selecting for partner drug resistance. The future of artemisinin resistance is uncertain; the mechanism underlying resistance has yet to be elucidated. With present levels of resistance artemisinins are still efficacious, albeit much more slowly than before. Whether higher levels of resistance can and will occur is uncertain. Nevertheless, given that previous pandemic spread of antimalarial resistance from South-East Asia killed millions, containing this threat is of the highest global health priority.
Artemisinin and its derivatives have become essential components of antimalarial treatment. These plant-derived peroxides are unique among antimalarial drugs in killing the young intraerythrocytic malaria parasites, thereby preventing their development to more pathological mature stages. This results in rapid clinical and parasitological responses to treatment and life-saving benefit in severe malaria. Artemisinin combination treatments (ACTs) are now first-line drugs for uncomplicated falciparum malaria, but access to ACTs is still limited in most malaria-endemic countries. Improved agricultural practices, selection of high-yielding hybrids, microbial production, and the development of synthetic peroxides will lower prices. A global subsidy would make these drugs more affordable and available. ACTs are central to current malaria elimination initiatives, but there are concerns that tolerance to artemisinins may be emerging in Cambodia.
Malaria is a major cause of anaemia in tropical areas. Malaria infection causes haemolysis of infected and uninfected erythrocytes and bone marrow dyserythropoiesis which compromises rapid recovery from anaemia. In areas of high malaria transmission malaria nearly all infants and young children, and many older children and adults have a reduced haemoglobin concentration as a result. In these areas severe life-threatening malarial anaemia requiring blood transfusion in young children is a major cause of hospital admission, particularly during the rainy season months when malaria transmission is highest. In severe malaria, the mortality rises steeply below an admission haemoglobin of 3 g/dL, but it also increases with higher haemoglobin concentrations approaching the normal range. In the management of severe malaria transfusion thresholds remain uncertain. Prevention of malaria by vector control, deployment of insecticide-treated bed nets, prompt and accurate diagnosis of illness and appropriate use of effective anti-malarial drugs substantially reduces the burden of anaemia in tropical countries.
No abstract is provided for this article.
No abstract is provided for this article.
Traditional interpretations of the evolution of animal societies have suggested that their structure is a consequence of attempts by individuals to maximize their inclusive fitness within constraints imposed by their social and physical environments. In contrast, some recent re-interpretations have argued that many aspects of social organization should be interpreted as group-level adaptations maintained by selection operating between groups or populations. Here, I review our current understanding of the evolution of mammalian societies, focusing, in particular, on the evolution of reproductive strategies in societies where one dominant female monopolizes reproduction in each group and her offspring are reared by other group members. Recent studies of the life histories of females in these species show that dispersing females often have little chance of establishing new breeding groups and so are likely to maximize their inclusive fitness by helping related dominants to rear their offspring. As in eusocial insects, increasing group size can lead to a progressive divergence in the selection pressures operating on breeders and helpers and to increasing specialization in their behaviour and life histories. As yet, there is little need to invoke group-level adaptations in order to account for the behaviour of individuals or the structure of mammalian groups.
In synthesizing recent studies of the relationships between British businesses and British governments during decolonization, the article takes issue with the gentlemanly capitalism paradigm. Imperial business and imperial government did not represent a cohesive elite; private and public agencies were frequently divided on key tenets of decolonization strategy; and, more often than not, it was broader macroeconomic and geostrategic factors rather than the agendas of particular business interests, that informed imperial policy.
The countries of the Greater Mekong subregion—Myanmar, Thailand, Laos, Cambodia, and Vietnam—have set a target of eliminating all Plasmodium falciparum malaria by 2025. Generous funding has been provided, principally by The Global Fund to Fight AIDS, Tuberculosis, and Malaria, to achieve this objective and thereby prevent the spread of artemisinin-resistant Plasmodium falciparum to India and Africa. As the remaining time to reach agreed targets is limited and future external funding is uncertain, it is important to be realistic about the future and spend what remaining funding is left, wisely. New, labour intensive, vertical approaches to malaria elimination (such as the 1-3-7 approach) should not be promoted as these are unproven, likely to be ineffective, costly, and unlikely to be sustainable in the most remote areas where malaria prevalence is highest. Instead, the focus should be on reducing the malaria burden more rapidly in the remaining localised high transmission foci with proven effective interventions, including mass drug administration. Well supported community-based health workers are the key operatives in controlling malaria, but their remit should be broadened to sustain the uptake of their services as malaria declines. This strategy is a sustainable evolution, which will improve rural health care while ensuring progress towards malaria elimination.
In polygynous, sexually dimorphic species, sexual selection should be stronger in males than in females. Although this prediction extends to the effects of early development on fitness, few studies have documented early determinants of lifetime reproductive success in a natural mammal population. In this paper, we describe factors affecting the reproductive success of male and female red deer (Cervus elaphus) on the island of Rum, Scotland. Birthweight was a significant determinant of total lifetime reproductive success in males, with heavier–born males being more successful than lighter ones. In contrast, birthweight did not affect female reproductive success. High population density and cold spring temperatures in the year of birth decreased several components of fitness in females, but did not affect the breeding success of males. The results confirm the prediction that selection on a sexually dimorphic trait should be greater in males than in females, and explain the differential maternal expenditure between sons and daughters observed in red deer. Differences between the sexes in the effects of environmental and phenotypic variation on fitness may generate differences in the amount of heritable genetic variation underlying traits such as birthweight.
