Background Chloroquine-resistant Plasmodium falciparum malaria is a major health problem, particularly in sub-Saharan Africa. Chloroquine resistance has been associated in vitro with point mutations in two genes, pfcrt and pfmdr 1, which encode the P. falciparum digestive-vacuole transmembrane proteins PfCRT and Pgh1, respectively. Methods To assess the value of these mutations as markers for clinical chloroquine resistance, we measured the association between the mutations and the response to chloroquine treatment in patients with uncomplicated falciparum malaria in Mali. The frequencies of the mutations in patients before and after treatment were compared for evidence of selection of resistance factors as a result of exposure to chloroquine. Results The pfcrt mutation resulting in the substitution of threonine (T76) for lysine at position 76 was present in all 60 samples from patients with chloroquine-resistant infections (those that persisted or recurred after treatment), as compared with a base-line p...

https://www.nejm.org/doi/pdf/10.1056/NEJM200101253440403

A molecular marker for chloroquine-resistant falciparum malaria.

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.

https://science.sciencemag.org/content/sci/320/5874/330.full.pdf

Qinghaosu (artemisinin): the price of success.

Increased efforts in antimalarial drug discovery are urgently needed. The goal must be to develop safe and affordable new drugs to counter the spread of malaria parasites that are resistant to existing agents. Drug efficacy, pharmacology and toxicity are important parameters in the selection of compounds for development, yet little attempt has been made to review and standardize antimalarial drug-efficacy screens. Here, we suggest different in vitro and in vivo screens for antimalarial drug discovery and recommend a streamlined process for evaluating new compounds on the path from drug discovery to development.

https://www.mmv.org/sites/default/files/uploads/docs/publications/7_-_ScreeningArticlePDF_7.pdf

Antimalarial drug discovery: efficacy models for compound screening

There are still approximately 500 million cases of malaria and 1 million deaths from malaria each year. Yet recently, malaria incidence has been dramatically reduced in some parts of Africa by increasing deployment of anti-mosquito measures and new artemisinin-containing treatments, prompting renewed calls for global eradication. However, treatment and mosquito control currently depend on too few compounds and thus are vulnerable to the emergence of compound-resistant parasites and mosquitoes. As discussed in this Review, new drugs, vaccines, and insecticides, as well as improved surveillance methods, are research priorities. Insights into parasite biology, human immunity, and vector behavior will guide efforts to translate parasite and mosquito genome sequences into novel interventions.

/pdf/malaria-progress-perils-and-prospects-for-eradication-hwwtkj4y7y.pdf

Malaria: progress, perils, and prospects for eradication

The burden of malaria is increasing, especially in sub-Saharan Africa, because of drug and insecticide resistance and social and environmental changes. Thus, there is an urgent need for vaccines, new drugs and insecticides. Parasite, mosquito and human genome projects are helping in the search for new control tools and international donors are developing new funding mechanisms that could make them available to poor countries. But these new tools will achieve their maximum impact only if additional resources are deployed to strengthen malaria research and control communities in countries where the new tools will be used.

Malaria in 2002

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(98)07367-X.pdf

Averting a malaria disaster.

ABSTRACT:Assumptions that bioethics was intended to focus only on a narrow set of issues related to research and health care are mistaken. The field of bioethics has long been focused on pressing contemporary issues, and it will play an unduly peripheral and less significant role than it could otherwise if it fails to focus on a broad set of issues, including human relations and the relationship of humans to nonhuman beings and the environment—and if it does not consider how to engage with others in addressing these issues. Bioethicists' traditional approaches, which emphasize an analytical role regarding values and goals, are important, but bioethicists also must include stakeholders in deliberations and consider how to translate goals into policy and practice.

M Danis

Papers

Averting a malaria disaster.

A Translational Role for Bioethics: Looking Back and Moving Forward