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A Nutty Idea for Controlling the Spread of Malaria
Abstract & Commentary
By Ellen Jo Baron, PhD, D(ABMM)
Professor of Pathology and Medicine, Stanford University; Medical School Director, Clinical Microbiology Laboratory, Stanford University Medical Center
Dr. Baron reports no financial relationships relevant to this field of study. Editor Stan Deresinski, MD, FACP, Clinical Professor of Medicine, Stanford, Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, serves on the speaker's bureau for Merck, Pfizer, Wyeth, Ortho-McNeil (J&J), Schering-Plough, and Cubist, does research for the National Institutes of Health, and sits on the advisory board for Schering-Plough, Ortho-McNeil (J&J), and Cepheid. Peer reviewer Connie Price, MD, Assistant Professor, University of Colorado School of Medicine, reports no financial relationships related to this field of study.
This article originally appeared in the April 2009 issue of Infectious Disease Alert.
Malaria ranks among the world's most important infectious diseases. The last year for which good statistics have been amassed, 2006, saw 250 million cases and at least one million deaths.1 The number of new malaria cases in the world each year dwarfs the same statistic for other well-known scourges.2 AIDS newly infected 2.7 million people and killed approximately 2 million in 2006.2 Tuberculosis also killed more people than did malaria (~ 2 million), but new infections were in the range of 4-5 million.2 Progression in malaria reduction can be attributed to several factors. The expanding use of insecticide-treated bed-nets has greatly reduced transmissions, particularly in sub-Saharan Africa.3 In the past five years, use of such insecticide-treated bed-nets has increased more than five times. Prevention of malaria reduces the need for antimicrobial treatment and, thus, conserves limited healthcare dollars. Widespread treatment of malaria with combination therapy, particularly utilizing the Chinese herbal medicine artemisinin, also has reduced both morbidity and mortality more than 50% over the last five years.4,5 Although the parasite has developed resistance to many Western antimicrobials in response to the widespread use, these drugs seem to regain efficacy when combined with artemisinin, a compound derived from a plant known as Sweet Wormwood (Artemisia annua).3,6 Used in ancient times by Chinese herbalists to treat fevers, the herb had fallen out of favor until a Chinese herbal pharmacopeia originally written in 340 A.D. was rediscovered in 1970.6
One important point often overlooked when malaria statistics are quoted is epitomized by the results of a study conducted several years ago in Ghana.7 Most diagnoses (from which prevalence statistics are derived) are clinical only. In carefully conducted trials using highly trained laboratory scientists, at best only 15% of cases diagnosed as malaria by physicians (and treated as such) were substantiated by laboratory test results.7 Other infections, such as bacterial meningitis and sepsis, were the primary true causes of the patients' symptoms. So although it is possible that malaria is not so prevalent as has been thought, it still affects an immense proportion of the populations in tropical countries of both hemispheres.1,2
Rapid diagnostic tests are being suggested for resource-poor areas to aid physicians' diagnoses. Unfortunately, a new study from Mali evaluating the efficacy of one rapid test (Paracheck-Pf) compared with laboratory microscopy for Plasmodium falciparum diagnosis found that although the test was 83% sensitive and 79% specific, the "treat all" strategy was more cost-effective than the "test and treat" strategy.8 This is one of several sandwich immunoassays used throughout the world. Recently a similar test was FDA-cleared for use in the United States. The Binax (Binax, Inc., Portland, Maine) is an immunochromatographic test in the same format as the Binax tests for respiratory syncytial virus and Streptococcus pneumoniae antigen in urine. A comparison of the malaria test to microscopy and the gold standard polymerase chain reaction showed the Binax to be 94% sensitive for the detection of P. falciparum malaria but only 84% for non-P. falciparum infections.9 Another evaluation of the Binax performed at the patient's bedside revealed a slightly less desirable 88% sensitivity for P. falciparum diagnosis.10 U.S. laboratories are advised to use the rapid test as an adjunct to current tests and not as a replacement. Better diagnostic tests are needed along with better prevention strategies. One creative approach to prevention deserves better publicity.
Malaria is spread by the bite of the female Anopheles mosquito. Mosquito abatement has been the basis of preventive efforts throughout much of the world.11 Removing standing water and treating ponds and other sites of larvae development with insecticides has been successful, but mosquitoes seem to develop resistance to the insecticides quickly.12 Global climate change also seems to have extended the range of Anopheles and other mosquitoes.13,14 A simple community-based but more sustainable mosquito larvae-killing method is needed. Recently, I worked side-by-side for a week in Mozambique with a Peruvian scientist who clearly was thinking outside of the box. Her story was so extraordinary that I wanted to write about it for this newsletter.
Dr. Palmira Ventosilla had a stroke of genius back in the mid-1990s. She was working with a strain of Bacillus thuringiensis (subspecies israelii), the very effective insect-larvae-destroying bacterium. Strains of this same species are used to kill pests throughout the American agricultural industry because of their virtual lack of toxicity to humans or any other organism and their single-minded attack on the larvae of insect pests. The bacterium is voracious in its destruction of mosquito larvae, but how could one provide sufficient cultures of BT1 to rural, economically challenged communities in the malaria-prone parts of the developing world? The organism itself is expensive when purchased directly from microbial suppliers. Microbiological skills, even incubators, were non-existent. The villagers had coconuts, though, so Dr. Ventosilla created a mini-incubator in a coconut! The method is deceptively simple. You provide swabs laced with the organism's spores to the villagers, and you teach the locals (mainly schoolchildren) to recognize mosquito larvae in water. One drills a hole in the top of a coconut, swishes the swab in the coconut milk, and seals the hole with candle wax. The coconuts are allowed to sit out in the sun for several days while the organisms multiply logarithmically in the warm coconut milk. The wax seal is then popped open and the Bacillus-laden coconut liquid is poured onto the offending water source. The bacteria remain active for at least 45 days. Nearly complete mosquito abatement ensued, and follow-up studies in a demonstration project in a Peruvian village have shown not only major reduction in malaria, but in dengue as well.12,15
Using low-tech methods to deliver high-tech solutions to global problems will be the path to the future we hope to realize. Understanding the local culture and working with it, rather than above it or against it, is reaping rewards in places from Peru to India. Dr. Palmira Ventosilla is showing us the way.