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Malaria Mortality (malaria + mortality)

Distribution by Scientific Domains

Medical Sciences	50%

Selected Abstracts

The mechanisms of resistance to antimalarial drugs in Plasmodium falciparum

FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2003
Jacques Le Bras
Abstract Drug-resistant malaria is primarily caused by Plasmodium falciparum, a species highly prevalent in tropical Africa, the Amazon region and South-east Asia. It causes severe fever or anaemia that leads to more than a million deaths each year. The emergence of chloroquine resistance has been associated with a dramatic increase in malaria mortality among inhabitants of some endemic regions. The rationale for chemoprophylaxis is weakening as multiple-drug resistance develops against well-tolerated drugs. Plasmodium falciparum drug-resistant malaria originates from chromosome mutations. Analysis by molecular, genetic and biochemical approaches has shown that (i) impaired chloroquine uptake by the parasite vacuole is a common characteristic of resistant strains, and this phenotype is correlated with mutations of the Pfmdr1, Pfcg2 and Pfcrt genes; (ii) one to four point mutations of dihydrofolate reductase (DHFR), the enzyme target of antifolates (pyrimethamine and proguanil) produce a moderate to high level of resistance to these drugs; (iii) the mechanism of resistance to sulfonamides and sulfones involves mutations of dihydropteroate synthase (DHPS), their enzyme target; (iv) treatment with sulphadoxine,pyrimethamine selects for DHFR variants Ile(51), Arg(59), and Asn(108) and for DHPS variants Ser(436), Gly(437), and Glu(540); (v) clones that were resistant to some traditional antimalarial agents acquire resistance to new ones at a high frequency (accelerated resistance to multiple drugs, ARMD). The mechanisms of resistance for amino-alcohols (quinine, mefloquine and halofantrine) are still unclear. Epidemiological studies have established that the frequency of chloroquine resistant mutants varies among isolated parasite populations, while resistance to antifolates is highly prevalent in most malarial endemic countries. Established and strong drug pressure combined with low antiparasitic immunity probably explains the multidrug-resistance encountered in the forests of South-east Asia and South America. In Africa, frequent genetic recombinations in Plasmodium originate from a high level of malaria transmission, and falciparum chloroquine-resistant prevalence seems to stabilize at the same level as chloroquine-sensitive malaria. Nevertheless, resistance levels may differ according to place and time. In vivo and in vitro tests do not provide an adequate accurate map of resistance. Biochemical tools at a low cost are urgently needed for prospective monitoring of resistance. [source]

Getting down to malarial nuts and bolts: the interaction between Plasmodium vivax merozoites and their host erythrocytes

MOLECULAR MICROBIOLOGY, Issue 5 2005
Julian Rayner
Summary Of the four Plasmodium species that routinely cause malaria in humans, Plasmodium falciparum is responsible for the majority of malaria mortality and consequently gets most of the headlines. Outside Africa, however, more malaria cases are caused by its distant cousin Plasmodium vivax, resulting in a daunting morbidity and economic burden for countries across Asia and the Americas. Plasmodium life cycles are complex, but the symptoms and pathology of malaria occur during the blood phase, when merozoites recognize and invade erythrocytes, initiating a developmental programme that culminates in lysis of the erythrocyte and release of multiple daughter merozoites. P. vivax merozoites are dependent on a single host cell receptor for erythrocyte invasion, the Duffy antigen receptor for chemokines, and humans that do not express this receptor on the surface of their erythrocytes are immune to P. vivax infection. This essential receptor,ligand interaction is addressed from both the host and parasite side in two papers in this issue of Molecular Microbiology, with important implications for plans to develop a P. vivax vaccine. [source]

Worms and malaria: noisy nuisances and silent benefits

PARASITE IMMUNOLOGY, Issue 7 2002
Mathieu Nacher
Summary The burden of malaria mortality has been a major evolutionary influence on human immunity. The selection of the most successful immune responses against malaria has been in populations concomitantly infected by intestinal helminths. Animal models have shown that coinfections with helminths and protozoa in the same host elicit a range of antagonist and synergistic interactions. Recent findings suggest similar interactions take place between helminths, Plasmodium falciparum and humans. However, as the threat of HIV and tuberculosis becomes a major selective force, what used to be a successful ecological system may now prove detrimental. Nevertheless, the understanding of the ecological forces at play may expose new intervention targets for malaria control, and give a new perspective on our shortcomings against the deadliest of human parasites. [source]

"Roll Back Malaria, Roll in Development"?

POPULATION AND DEVELOPMENT REVIEW, Issue 1 2009
Reassessing the Economic Burden of Malaria
Recent efforts to mobilize support for malaria control have highlighted the economic burden of malaria and the value of malaria control for generating economic development. These claims have a long history. Beginning in the early twentieth century, they became the primary justification for malaria-control programs in the American South and in other parts of the globe, including British India. Economists conducted none of these studies. Following World War II and the development of new anti-malarial drugs and pesticides, including DDT, malaria control and eradication were increasingly presented as instruments for eliminating economic underdevelopment. By the 1960s, however, economists and demographers began to raise serious substantive and methodological questions about the basis of these claims. Of particular concern was the role of rapid population growth, resulting in part from the decline of malaria mortality, in undermining the short-term economic gains achieved through malaria control. Despite these concerns, malaria continues to be presented as an economic problem in the work of Jeffrey Sachs and others, justifying massive investments in malaria control. The methodological basis of these claims is examined. The paper concludes that while malaria takes a dreadful toll in human lives and causes significant economic losses for individuals, families, and some industries, the evidence linking malaria control to national economic growth remains unconvincing. In addition, the evidence suggests that there are potential costs to justifying malaria-eradication campaigns on macroeconomic grounds. [source]