African children under 5 years of age bear the main burden of global malaria mortality. Seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine (SP) plus amodiaquine (AQ) given monthly during the rainy season is a highly effective malaria intervention for children aged between 3 months and 5 years living in the Sahel region, a region of intense but seasonal malaria transmission. This intervention is now being considered for other regions of Africa where malaria parasites are more drug resistant. Dihydroartemisinin-piperaquine (DP), an artemisinin-based combination therapy (ACT), has proved to be highly effective and well tolerated in intermittent preventive treatment in pregnant women and children. This combination may be a suitable alternative for SMC. Understanding the safety, pharmacokinetic and pharmacodynamic properties of antimalarial combination therapies is crucial in optimising dosing.
In polygynous mammals, most variance in male reproductive success is expected to result from competition between males, and the role of female behavior remains poorly understood. Contests between red deer males during the annual rut are one of the most famous examples of male–male competition. However, anecdotal evidence suggests females in estrus make substantial movements, changing harems, and potentially disrupting the outcome of male contests. In other polygynous mammals, such movements have been interpreted as evidence of female mating preferences. Here, we use 34 years of detailed observational data on wild red deer to show that 43% of estrous females are found in different harems between successive observations and that 64% of such females make substantial movements (up to 4 km) when this occurs. Approximately 45% of these movements result in the male into whose harem a female moved fathering her offspring. We then test whether females move nonrandomly with respect to male phenotype, consistent with the hypothesis that females move to mate with preferred males. Although in general, females were more likely to be found in larger harems and the harems of younger males after harem changes, these effects were not specific to estrous females. Further, estrous females were not more likely to be found in the harems of less related males. We therefore find little support for the idea that estrous females move between harems to mate with a preferred male; as a result, the reasons females make such extraordinary movements when in estrus remain unclear.
No abstract is provided for this article.
In the Soay sheep population of Hirta (St. Kilda), high winter mortality occurs every 3-4 years following summers when population density exceeds 2.2 sheep ha −1 . During these die-offs, more than 50% of adults, 70% of yearlings and 90% of lambs die and population density falls by around 65%. This paper investigates the extent to which density-related changes in early growth might be responsible for fluctuations in over-winter survival and population size
No abstract is provided for this article.
It would indeed be wonderful if concerns over artemisinin resistance were a false alarm, or that the current levels of resistance could not be exceeded.1 However, are we “wrong to be distracted” by increasing evidence of resistance to the key drug for the treatment of severe and uncomplicated falciparum malaria emerging from the very place where resistance to chloroquine and sulfadoxine-pyrimethamine emerged before? Our slow and ineffective responses to those disasters cost the lives of millions of people—mainly children in Africa. Only a small fraction of the world's malaria burden occurs in mainland South-East Asia, yet that is where the resistance comes from. In an increasingly interconnected world, ignoring the potential for rapid spread to infect India and Africa seems worse than unwise. That is why everything that can be done should be done to curb spread and eliminate foci of artemisinin resistance in Asia. Now to those other “messy inconsistencies”; in areas where parasite clearance rates have slowed markedly failure rates to artemisinin combination treatments (ACTs) have risen, and have prompted changes in policy. On the North West border of Thailand failure rates with artesunate-mefloquine now exceed 30%. The apparent paradox of reduced clinical efficacy without marked changes in in vitro susceptibility is explained readily by loss of ring-stage susceptibility to artemisinins without major changes in susceptibility of the trophozoite and schizont stages2; this results in delayed parasite clearance and reduced overall parasiticidal effect. Most in vitro tests evaluate predominantly the drug susceptibility of these more mature parasite stages. The second point that worse resistance to artemisinin may not occur is something we should all hope for, but certainly should not rely upon. The third point that ACT failures can result from resistance to the partner drug is true, but does not explain current therapeutic responses. When ACTs were first introduced in 1994 failure rates with mefloquine alone on the North West Thailand border were approaching 50%, yet the additional 3 days of artesunate reduced this to a failure rate of ∼5%.3 Today susceptibility to mefloquine has returned to levels similar to those in 1994, yet failure rates are six times higher. Clearly this is because of resistance to artemisinin and not just to mefloquine. Yet the two are linked as declining artemisinin susceptibility means that the partner drug in an ACT must remove a greater proportion of the infecting parasites to effect cure, and this increases the selection pressure for the emergence of partner drug resistance. Given the potentially devastating consequences of losing our front-line antimalarial drugs, raising the alarm is surely the right thing to do. Let us hope the response is effective for, if I remember correctly, the wolf did eat the flock.
