Editor's Note: Science Scan is a roundup of recently published biotechnology-relevant research.
An estimated 12 million people are infected with Leishmania parasites worldwide. Usually the immune system controls the infection and prevents development of leishmaniasis, a disfiguring and sometimes fatal disease.
But for some people, such as those with AIDS who have a suppressed immune system, the parasites become active and trigger the disease. In fact, leishmaniasis is a common complication of AIDS in endemic tropical regions including the Mediterranean basin, southern Europe, Asia, Africa and Latin America.
Medical care for the parasitic infection is either extremely expensive by Third World standards ($140 for a single treatment of leishmaniasis) or is nonexistent. Cutaneous leishmaniasis has occurred among U.S. military personnel operating in the Middle East.
Persistent parasite infections are usually difficult to study because it often may take six months to a year before research can begin. Parasitologists at Washington University Medical School in St. Louis side-stepped this hang-up by developing a mutated Leishmania parasite incapable of causing disease. This strategy enabled the team to start studying the animals about one week after infection. Their report, in Science dated Aug. 29, 2003, carries the title "Persistence without pathology in phosphoglycan-deficient Leishmania major."
The co-authors tested the engineered parasites in sand flies, insects that are responsible for transmitting the parasites to humans. They also examined the parasites in immune cells called macrophages. Those normally protect the body by scavenging it of waste, but are the cells that house the Leishmania parasites that cause disease in mammals.
Compared to normal parasites, the mutants showed a 10-fold lower survival rate in the sand flies after three days. At that point they were completely eliminated. They were also unable to survive in macrophages. Next, the team injected the parasites into mice that were genetically susceptible to leishmaniasis. As expected, the animals did not get sick, suggesting that the parasites had not survived. Surprisingly, though, live parasites were found in tissue samples from these mice.
Inasmuch as the parasites did not persist in macrophages, the researchers are now hunting for cells that are hospitable to the parasites. They are also looking into whether mutant parasites may help develop a vaccine against the ubiquitous disease.
For bygone centuries, sand flies had been thrusting their pointy proboscises into the human epidermis and withdrawing enough blood for their nutritional needs. In 1824, in Bengal, they added parasites to this blood suction. The tiny Leishmania donovani parasites swam into the bloodstreams of the Bengali merchants and their families. Soon kala-azar or dum-dum fever, as the disease was then called, was attacking the veins of humans in cities all along the Ganges River.
Another round of sand fly-delivered kala-azar struck Assam, India, in 1918. That outbreak killed more than 200,000 people. It made a return visit in 1944. An up-to-date electronic medical dictionary lists 25 varieties of leishmaniasis, from A to Z - acute to zoonetic.
Famous Antiretroviral Drug Cocktails Against HIV, AIDS Tapped For Added Gig - Curbing TB
Antiretroviral (ARV) drugs are famous for curbing HIV infection and stalling death from AIDS. These drugs have the added potential to halt the rapid growth of HIV-related tuberculosis (TB). Their immediate role in TB control will be to enhance the quality of treatment for HIV-infected TB patients.
Using ARV drugs to prevent new cases of TB will prove more difficult, suggests a report by communicable disease specialists at the World Health Organization in Geneva. Its title in Science dated Aug. 14, 2003, reads "Antiretroviral drugs for tuberculosis control in the era of HIV/AIDS."
Its authors set out to determine the potential, community-level impact of ARV drugs on TB. Their findings may be of particular interest in less-developed areas of the world where HIV threatens TB control. No low- or middle-income country (except Brazil, perhaps) comes close to satisfying the public health conditions necessary to allow antiretroviral treatments to substantially curb new TB cases, the Science paper suggests.
It leads off by noting that "HIV/AIDS has dramatically increased the incidence of tuberculosis in sub-Saharan Africa where up to 60 percent of TB patients are co-infected with HIV and each year 200,000 TB deaths are attributable to HIV co-infection. Now HIV threatens TB control in Asia, Eastern Europe and Latin America. Antiretroviral drugs can prevent TB by preserving immunity but cohort analysis shows that early therapy, plus high levels of coverage and compliance, will be needed to avert a significant fraction of TB cases. However," it concludes, "ARVs could enhance the treatment of TB while TB programs provide an important entry point for the treatment of HIV/AIDS."
New Molecules Enter Arena Of Feeding, Body Weight Gain - So Far In Mice
Oleylethanolamide (OEA) is a naturally occurring lipid (fat-soluble) that regulates satiety and body weight. Feeding OEA to animal models controls appetite and reduces body weight gain in wild-type mice, but not in mice deficient in an OEA receptor called PPAR-alpha. The current issue of Nature, dated Sept. 4, 2003, carries the title "Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR." Its authors are at the University of California at Irvine.
Molecules designed to target this receptor may prove to be effective treatments for eating disorders, the co-authors suggest. OEA is known to regulate feelings of "fullness" and body weight. In normal situations, OEA controls the expression of several genes that are downstream of PPAR-alpha. It initiates the production of proteins involved in lipid metabolism and represses an enzyme that may stimulate feeding effects.
"Our results," the paper concludes, "identify an unexpected role for this nuclear receptor in regulating behavior, and raise possibilities for the treatment of eating disorders."