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By Carol A. Kemper, MD, FACP
Sources: Newton P, et al. Lancet. 2001;357:1948-1950; Wall Street Journal. June 26, 2001;International section: A16.
Artesunate, derived from the Chinese herb of the same name, is one of the oldest antimalarials in southeast Asia, where it is frequently used in the suppression of falciparum malaria. Most artesunate in southeast Asia is manufactured by Guilin Pharma in China. Studies have shown that quality control standards for the manufacturing and distribution of many antimalarials in southeast Asia are often lacking. Pills and tablets are often found to contain inadequate or expired drug.
Newton and colleagues found evidence of a widespread and large-scale manufacturing and distribution operation of counterfeit artesunate in southeast Asia. Overall, 39 of 104 (38%) samples purchased from shops and pharmacies in Myanmar, Cambodia, Vietnam, Laos, and western Thailand contained no artesunate. The problem is so significant Newton et al report that one organization, which was thrilled to lay their hands on 100,000 tablets of artesunate, subsequently discovered they were fake.
Newton et al determined that counterfeit drug could be distinguished from the real thing based on a number of features in the packaging, including the printing, the bar code, an inadequate or absent company hologram, as well as lower cost. Many fake pills had the "AS" logo stamped only on 1 side of the tablet—not both—as with the real drug. Interestingly, the fake artesunate has been manufactured with a bitter taste, reminiscent of chloroquine (compared to the chalky taste of artesunate), as if the manufacturer wanted people to believe they were taking a "true" antimalarial. A "red dye" test, which is based on a reaction between an alkali-decompensation product of artesunate and a salt, can also differentiate fake from true drug.
The European union is currently sponsoring a program to combat the distribution of fake artesunate in SE Asia, which has been field-tested with success in 2 rural provinces of Cambodia. Artesunate and mefloquine are packaged together in a tamper-proof box, intended to thwart the separate sale of the drugs at greater profit. They are also field-testing a rapid test for malaria right at the pharmacy, where most people purchase their drugs without first seeing a doctor. However, Newton et al stressed the need for more stringent governmental control, pointing out that while there have been no prosecutions for the manufacture, distribution, or sale of fake antimalarials, Vietnam has given prison sentences of up to 20 years for illegal trafficking of fake Viagra!
Source: Nurozler F, et al. Ann Thorac Surg. 2001;71:614-618.
Nurozler and colleagues from Columbia University in New York report on their 10-year experience with fungal infection in 165 persons who received implantable left ventricular assist devices (LVAD). A total of 112 patients received vented electric devices (VED) and 53 patients received pneumatic devices (PD). Almost half of the patients received antibiotics for complicating bacterial infections. While only 5 patients had evidence of fungal infection at the time the devices were implanted, 37 (22.4%) patients subsequently developed fungal infections, more than 90% of which were candidal. Device-related infections were found in 18 (10.9%), with positive cultures of the LVAD pocket, mediastinum, drive-line site, or of the explanted device. Patients with pneumatic devices were more likely to have drive-line infection. In contrast, patients with VEDs were more likely to have pocket and mediastinal infections.
Fungal endocarditis occurred in 5 (3%) patients, all of whom had positive fungal cultures from the blood-contacting surfaces of the device at explantation. Three of these were due to C albicans, 1 due to C parapsilosis, and 1 developed sepsis from Syncephalastrum racemosum. All 5 infections were difficult to diagnosis; echocardiograms were negative for vegetations or pannus formation in all 5 cases (most likely because of the reflective properties of the devices that limit the sensitivity of echo). Only 1 patient had positive blood cultures, despite gross histologic evidence of complicating fungal infection of the device itself in 2 cases. One patient died acutely when the outflow tract of the device became obstructed from fungal matter, and another had an embolic cerebrovascular event with evidence of a large fungal ball obstructing the outflow tract at explantation, although he had no hemodynamic signs of outflow obstruction. Clinical signs of fungal infection were nonspecific, and included fever, weight loss, and sepsis, although fever may not always be present.
In addition to the presence of a prosthetic device in immediate contact with blood, LVAD may significantly affect cell-mediated immunity. Given the high rate of fungal colonization and severe infection in patients with LVAD, patients with continued fever or sepsis should probably receive Amphotericin B plus broad-spectrum antibacterials.
Carol Kemper is Clinical Associate Professor of Medicine, Stanford University Division of Infectious Diseases, Santa Clara Valley Medical Center; Section Editor of Updates and HIV, and Associate Editor of Infectious Disease Alert.