Economist, Oct 10, 2015 (II)

choi

There is no need to read any of the reports in this posting.

(1) Leaders  | Eradicating Disease; Viral and parasitic diseases are not only worth killing off, they are also increasingly vulnerable
(“The other half [of 2015 Nobel Prize for Physiology or Medicine] was won by the woman who came up with an answer to drug resistance in malaria -- a medicine called artemisinin, which has been crucial to the success of the recent push against the disease. (This time, alert to the risk of resistance, doctors have formulated it with other drugs to create combination therapies that natural selection finds hard to get around”)

(2) Malaria eradication | Breaking the Fever; The end is in sight for one of humanity’s deadliest plagues. (a “briefing”)
http://www.economist.com/news/br ... gues-breaking-fever

Quote:

largely through public health and aggressive identification and treatment of patients (thus stop infection from spreading) and not through medical or pharmaceutical breakthroughs, “Swaziland [is on] the threshold of becoming the first malaria-free country in sub-Saharan Africa, the part of the world most blighted by the disease. Since 2000, malaria deaths around the world have fallen by nearly half. The steepest drop has come in sub-Saharan Africa, where 90% of fatalities occur. Malaria still kills around 450,000 people each year—most of them children in Africa.

“Bed nets treated with insecticide are among the more effective and widespread low-cost measures. Most countries distribute them free.

“After decades of near misses, a vaccine is almost available. RTS,S (sic), the first to pass all stages of clinical trials, awaits WHO approval; European regulators nodded it through in July. Developed by GlaxoSmithKline, a drugs firm, and the Malaria Vaccine Initiative, an American non-profit organisation, RTS,S works, but not terribly well. It cuts the number of malaria episodes among infants and toddlers, typically one to five a year, by 36% over four years. It is not known how it will perform over a longer period.  That is about half the effectiveness needed for such a vaccine to become a potent weapon of eradication by greatly diluting the human reservoir of the parasite, says James Beeson of the Burnet Institute, an Australian research outfit. An ideal vaccine, says Mr Beeson, would have two components: one would stop infections in humans or stop infected humans from becoming sick; and the other would target transmission by making mosquitoes unable to pass on the malaria parasite. Separate vaccines for each of these tasks are in the pipeline but none is yet undergoing large-scale clinical trials.

“Swaziland’s eradicators are busiest straight after Christmas, when the Mozambicans who work on the country’s sugar plantations return from visits across the border. Half Swaziland’s malaria cases are now imported.

(3) The 2014 Nobel science prizes  | Wisdom, Ancient and Modern; This year’s Nobels go to the inventors of two anti-parasite drugs, the discoverers of how cells repair their DNA, and the researchers who showed neutrinos have mass.

Quote:

"To this day, some of the best-known, including aspirin, morphine and digitalis, are either made from plants or based on plant molecules. So the fact that artemisinin, the newest treatment for malaria, is derived from a plant used for that purpose in China for well over 2,000 years should be no surprise.

"Artemisinin has played a pivotal role in the halving, since 2000, of the number of deaths inflicted by malaria. Dr Tu [Youyou] was therefore a laudable winner of a share in this year’s Nobel prize for physiology or medicine. She took an idea she had developed originally in a secret Chinese project designed to help keep North Vietnamese soldiers malaria-free during the Vietnam war, and pushed it forward to become the saviour of a field in which existing drugs were becoming less and less useful, because of the evolution of resistance to them by the parasite that causes malaria.

choi

The following is a summary of current understanding on mechanism of action for two drugs that draws attention from the 2015 Nobel Prize for medicine.

(a) Mbengue A et al, A molecular mechanism of artemisinin 青蒿素 resistance in Plasmodium falciparum malaria. Nature 520, 683–687 (Apr 30, 2015)
http://www.nature.com/nature/jou ... ll/nature14412.html
("there is no consensus on biochemical targets of artemisinin")
(b) satoshi ŌMURA 大村 智 isolated avermectin from Streptomyces avermitilis (a kind of 鏈黴菌). For testing, he sent it to Merck where William C Campbell worked. Avermectin "enhanc[es] the effects of glutamate at the invertebrate-specific glutamate-gated chloride channel * * * This causes an influx of chloride ions into the cells, leading to hyperpolarisation [you do not have to know the meaning of this word] and subsequent paralysis of invertebrate neuromuscular systems; comparable doses are not toxic for mammals because they do not possess glutamate-gated chloride channels." Wikipedia.  Avermectin is used to treat mammal diseases caused by nematodes 線蟲 or roundworm 蛔蟲.

Note: A glutamate-gated chloride channel is a chloride channel (channel that allows passage of chloride ions but no others) that will open (and allow passage) when glutamate attaches itself to the channel.