Chloroquine chemical structure
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Chloroquine

Chloroquine is a commonly used form of medication against malaria. As it also mildly suppresses the immune system, it is used in some autoimmune disorders, such as rheumatoid arthritis. more...

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Pharmacology

It has a very high volume of distribution, as it diffuses into the body's adipose tissue.

Mechanism of action

Inside the red blood cells, the parasite must degrade the hemoglobin for the acquisition of essential amino acids, which the parasite needs to survive and multiply inside the cell.

During this process, the parasite produces the toxic and soluble molecule heme. To avoid destruction by this molecule, the parasite aggregates heme to form hemozoin, an insoluble non-toxic molecule. Hemozoin formation is mediated by phospholipids as well as histidine-rich proteins Pfhrp-2 and Pfhrp-3.

Chloroquine interferes with binding of heme to histidine-rich proteins or lipids and prevents the formation of hemozoin, which in turn leaves heme in an uncrystallised form. This has a toxic effect to the parasite, and is therefore killed by this molecule.

The effectiveness of chloroquine against the parasite has declined as some resistant forms of the parasite can effectively neutralize the drug by developing a mechanism that drains chloroquine away from the key area, preventing heme from reaching the necessary concentration.

Against rheumatoid arthritis, it operates by inhibiting lymphocyte proliferation, phospholipase A, release of enzymes from lysosomes, release of reactive oxygen species from macrophages, and production of IL-1.

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Who's to blame? The tsunami's aftermath
From National Review, 2/14/05 by Roger Bate

Galle, Sri Lanka

THE last time I was here in Galle, England had just played a great cricket match against the Sri Lankans, the local economy was bustling, and the great threat--from the Tamil Tiger rebels--was losing its force. But today, the cricket pitch lacks a single blade of grass, the economy is in tatters, and there are over 31,000 dead from the tsunami. The only things that remains the same in this southern port--75 miles southeast of Colombo--are the heat and humidity. One alarming new difference is that malaria is back, and is poised to strike down still more of the children, many orphaned, of this wretched place. It can be stopped, but only if ill-informed prejudice against DDT, the insecticide, is dropped.

As I fly over the port, I think the devastation does not look as bad as the pictures I've seen of Banda Aceh, Indonesia, which Secretary of State Colin Powell described as resembling the aftermath of a nuclear explosion. But Galle is still a terrible mess. Though Aceh, as the worst-affected region, is rightly getting most of the attention, private-aid groups have acted swiftly in Galle as well. Thanks to their food drops and water provisions, its inhabitants have managed to survive the immediate aftershocks of the tsunami's devastations. But the malaria-control program is being compromised by outdated thinking, especially from the world's leading health and government-aid agencies.

The prime example of their folly is found in a paper, "Malaria Risk and Malaria Control in Asian Countries Affected by the Tsunami," in which the World Health Organization (WHO) outlines its policy for the affected region. While a relatively sound document, it does perpetuate mistakes, which are then copied by everyone else operating in Sri Lanka and the rest of Asia.

In Sri Lanka, malaria is transmitted by the female anopheles culcifacies mosquito. The species breeds in rock pools and rice fields, and is a fairly efficient vector of the disease. Historically, the primary method of malaria control has been Indoor Residual Spraying (IRS)--the spraying of house walls with tiny amounts of an insecticide, usually DDT. IRS often kills mosquitoes, but more important, it creates a barrier between man and mosquito. Studies show the vast majority of mosquitoes won't enter a DDT-sprayed building, and this chemical barrier prevents transmission of the disease, much as prophylactic drugs or bed nets do, but more cheaply. Such an approach was highly successful in Sri Lanka. Owing to DDT, malaria rates fell from three million cases a year in the 1940s to fewer than 50 in 1963.

But then environmental pressures against DDT led to its abandonment, first in Western countries and then in most other parts of the world. Although it was obvious that it was the massive use of DDT in farming, not the small amounts used in public-health applications, that caused the environmental problems, the issue of scale was ignored by policymakers.

Aid agencies' failure to fund DDT was not the only problem. Studies showed that Sri Lankan mosquitoes may be developing resistance to DDT, which meant that some of them would not be killed by the insecticide. Even the WHO report says Sri Lanka's malaria vectors have been considered DDT-resistant for many years. But DDT's main role is as a repellent, not as a toxic agent. Houses sprayed with DDT repel far more mosquitoes than any other insecticide tested and so remain effective even when resistance is substantial. This information, although known by health entomologists, is ignored by the WHO, which has adopted the anti-DDT environmentalist agenda. The WHO advises using alternative insecticides--although the organization buys precious few even of these.

The organization spent the vast majority of its $980,000 Sri Lankan tsunami-related resources on bed nets (about $780,000), and about $100,000 on spraying of the organophosphate insecticide Malathion (often used to combat West Nile Virus-carrying mosquitoes). Unfortunately, this Malathion spraying is not the most effective indoor variety--the kind in which one spray provides months of protection--but rather the kind known as "fogging": the external spraying of a cloud of insecticide to kill adult mosquitoes. Even the WHO admits that fogging is not a very useful approach. It does, however, look good on TV, and demonstrates that action is taking place.

The WHO is also supplying about $70,000 of old drugs, and pharmaceutical company Novartis has donated over $40,000 worth of its new anti-malarial drug, Coartem, which has zero failure rate in Sri Lanka. (The old drugs still just about work, although the oldest, chloroquine, is losing its efficacy in Sri Lanka, and should not really have been purchased by WHO.) WHO actors on the ground, along with other aid-agency personnel, are doing the best they can, but they are hampered by an official policy that is harmful. Unfortunately, to speak out against it is to risk one's job, so criticisms rarely occur. The cost can be measured in Sri Lankan lives lost.

Though Janaka Tillakeratne lost his cafe to the tsunami, he has kept his family safe and free from major disease. But he has no bed nets for his family and would like his house to be sprayed to lower his children's risk of disease, be it malaria or dengue or any other fevers spread by bugs thriving in the post-tsunami chaos; but extensive indoor spraying won't be happening any time soon. As I left for the airport he smiled and told me to come back and watch some cricket here again. "Perhaps in a year when the pitch is repaired," he said. "And make sure you buy produce from my new shop," which he is already planning. I walked back and handed him my remaining supply of Coartem; it was the least I could do.

The tragedy of the tsunami is obvious and it was largely unavoidable. But malaria deaths could be significantly reduced if only health agencies would do the politically incorrect--but morally correct--thing and spray DDT and other long-term insecticides. If this disaster doesn't persuade them to change, nothing will.

Mr. Bate is a health economist with Africa Fighting Malaria and a fellow at the American Enterprise Institute.

COPYRIGHT 2005 National Review, Inc.
COPYRIGHT 2005 Gale Group

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