Featured Research

from universities, journals, and other organizations

Revived Drug Prevents Malaria, Skirts Drug Resistance

Date:
September 27, 1999
Source:
Johns Hopkins Medical Institutions
Summary:
A chemical ranked with the second-string players in the world's continuing contest with malaria has reappeared as a new drug, apparently capable of preventing the disease. Paired with an older, standard drug, it provides protection with an unusually small risk of drug resistance.

A chemical ranked with the second-string players in the world's continuing contest with malaria has reappeared as a new drug, apparently capable of preventing the disease. Paired with an older, standard drug, it provides protection with an unusually small risk of drug resistance.

In a study in the September American Journal of Tropical Medicine and Hygiene, researchers at Johns Hopkins describe how the drug atovaquone was 100 percent effective in keeping volunteers bitten by mosquitoes carrying Plasmodium falciparum, the parasite responsible for fatal forms of malaria, from developing the disease.

"Atovaquone attacks the parasite at a different point in its life cycle from other drugs -- one that reaches the parasite sooner," says Theresa A. Shapiro, M.D., Ph.D., the clinical pharmacologist who led the Hopkins team. Further, pairing atovaquone with proguanil, an older malaria-fighting drug, "should greatly raise our chances of preventing malaria while avoiding the drug resistance that now plagues its treatment. Clobbering parasites at two places," Shapiro says, "is greater insurance that you clean them out."

Drug resistance occurs when a few parasites in their human hosts manage to survive therapy. The parasites then prosper and dominate as causes of disease. Malaria researchers report that drug-resistant forms of the parasite infest 80 percent of countries with the disease.

Atovaquone's different approach may skirt another stumbling block in malaria prevention: keeping patients on the drugs. With current preventives, travelers must take them weeks after a visit to a malaria-carrying country. "With atovaquone, travelers should be able to take their last dose as they leave," says Shapiro.

In the study, 12 volunteers were started on atovaquone -- at either a high or a low dose -- while four volunteers received a placebo drug. All were then exposed to and bitten by five mosquitoes heavily infected with the malaria parasite. "If you plan to expose people to falciparum malaria, especially on an outpatient basis," says Shapiro, "you'd better know what you're doing. We carefully screened for volunteers who knew what was going on, who understood their consent papers, who knew the risks they were taking and who realized the importance of being 100 percent compliant in their follow-up visits. We needed people who went into this with their eyes open."

The volunteers reported daily to a Hopkins clinic for three weeks, then somewhat less frequently for another eight weeks, getting blood tests for the parasite as well as an interview geared to pick up symptoms.

The blood tests included new methods sensitive to human red blood cells carrying parasites as well as conventional microscopic searches for the parasites in blood. As a more precise check, the researchers also used PCR (polymerase chain reaction) assays sensitive to parasite DNA.

After two weeks, the four volunteers not on atovaquone developed malaria, while those on the drug had no signs of infection. (The daily blood tests caught the malaria at its earliest stages in the four with the disease; they were promptly put on standard drug therapy and declared disease-free three days later. Follow-up testing a year later showed no disease.)

Further, says Shapiro, failure of the parasites to survive the lowest dose of atovaquone is one of several signs that the drug attacks the parasites early on, when they move into the liver in the first stage in their life cycle. Other drugs typically act later, only after the parasites have reproduced in the liver 30,000-fold, migrated into red blood cells and entered the bloodstream as the blood cells rupture.

Atovaquone, whose chemical structure is unusual, belongs to a class of anti-malarials called hydroxy-naphthoquinones originally readied during World War II. Most of the drugs in that group proved too toxic or too quickly broken down in the body. "They lost out when more benign and easily synthesized drugs such as chloroquine appeared," Shapiro says. But atovoquone, an offshoot developed later in the 1970s, had promise because it was the least toxic.

It crawled on a slow track until recently, when drug companies resurrected it as a therapy for the Pneumocystis infections that give AIDS patients pneumonia. "Atovoquone is a survivor," says Shapiro. "Now here it is again."

The research was funded by Glaxo Wellcome, an NIH grant and the Burroughs Wellcome Fund. Glaxo Wellcome is preparing to donate the combined form of atovaquone and proguanil to a non-profit foundation that will distribute the drug, with tight restrictions, in malaria-endemic countries. "If you have a new approach to drug resistance," says Shapiro, "you can't squander it. You can't throw the drug around carelessly. We've seen what happens when we do that."

Other Hopkins researchers in the study are Channa D. Ranasinha, M.D.(a postdoctoral fellow no longer at Hopkins), Nirbhay Kumar, Ph.D., and Patricia Barditch-Crovo, M.D.

The article is in the American Journal of Tropical Medicine 60(5), 1999, pp.831-836.Photographs are available showing parasites breaking out of red blood cells, of humans being inoculated by mosquitoes.

Related Web site: http://www.cdc.gov/ncidod/dpd/list_mal.htm -- This site tells the status of malaria worldwide, and gives statistics and current therapies.

--JHMI--

Johns Hopkins Medical Institutions' news releases are available on an EMBARGOED basis on EurekAlert at http://www.eurekalert.org, Newswise at http://www.newswise.com and from the Office of Communications and Public Affairs' direct e-mail news release service. To enroll, call 410-955-4288 or send e-mail to bsimpkins@jhmi.edu.

On a POST-EMBARGOED basis find them at http://hopkins.med.jhu.edu, Quadnet at http://www.quad-net.com and ScienceDaily at http://www.sciencedaily.com.


Story Source:

The above story is based on materials provided by Johns Hopkins Medical Institutions. Note: Materials may be edited for content and length.


Cite This Page:

Johns Hopkins Medical Institutions. "Revived Drug Prevents Malaria, Skirts Drug Resistance." ScienceDaily. ScienceDaily, 27 September 1999. <www.sciencedaily.com/releases/1999/09/990924120039.htm>.
Johns Hopkins Medical Institutions. (1999, September 27). Revived Drug Prevents Malaria, Skirts Drug Resistance. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/1999/09/990924120039.htm
Johns Hopkins Medical Institutions. "Revived Drug Prevents Malaria, Skirts Drug Resistance." ScienceDaily. www.sciencedaily.com/releases/1999/09/990924120039.htm (accessed July 31, 2014).

Share This




More Health & Medicine News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Concern Grows Over Worsening Ebola Crisis

Concern Grows Over Worsening Ebola Crisis

AFP (July 30, 2014) Pan-African airline ASKY has suspended all flights to and from the capitals of Liberia and Sierra Leone amid the worsening Ebola health crisis, which has so far caused 672 deaths in Guinea, Liberia and Sierra Leone. Duration: 00:43 Video provided by AFP
Powered by NewsLook.com
At Least 20 Chikungunya Cases in New Jersey

At Least 20 Chikungunya Cases in New Jersey

AP (July 30, 2014) At least 20 New Jersey residents have tested positive for chikungunya, a mosquito-borne virus that has spread through the Caribbean. (July 30) Video provided by AP
Powered by NewsLook.com
Xtreme Eating: Your Daily Caloric Intake All On One Plate

Xtreme Eating: Your Daily Caloric Intake All On One Plate

Newsy (July 30, 2014) The Center for Science in the Public Interest released its 2014 list of single meals with whopping calorie counts. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

    Environment News

    Technology News



      Save/Print:
      Share:

      Free Subscriptions


      Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

      Get Social & Mobile


      Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

      Have Feedback?


      Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
      Mobile: iPhone Android Web
      Follow: Facebook Twitter Google+
      Subscribe: RSS Feeds Email Newsletters
      Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins