According to the World Health Organization, infectious diseases are a significant cause of morbidity and mortality worldwide, accounting for approximately 50% of all deaths in tropical countries. While such statistics may not come as a surprise in developed nations, it should be noted that infectious disease mortality rates are also increasing in Western nations. For example, in the United States, death from infectious disease ranked fifth in 1981, but by 1992, it was the third leading cause of death, representing an increase of 58%. Contributing to this increase is the HIV/AIDS pandemic and resultant secondary infections, as well as an increase in antibiotic resistance in both nosicomial and community-acquired infections. Since the first case of penicillin-resistant Staphylococcus aureus, the problem of antimicrobial resistance has become a serious threat to public health with economic, social, and medical implications that are global in scope and cross all environmental and ethnic boundaries. Multidrug-resistant tuberculosis is no longer confined to any one country or to those co-infected with HIV, but has appeared in locations as diverse as Eastern Europe, Africa, and Asia, among healthcare workers and in the general population. Penicillin-resistant pneumococci and drug-resistant malaria are on the rise, disabling and killing millions of children and adults every year. In 1990, almost all cholera isolates gathered around New Delhi, India, were sensitive to inexpensive, first-line drugs such as furazolidone, ampicillin, co-trimoxazole, and nalidixic acid. However, by 2000, most of the formerly effective drugs were useless and no longer able to contain cholera epidemics. Furthermore, the emergence of hitherto unknown disease-causing microbes poses an enormous threat to public health. Such negative health trends call for a new global initiative for the development of new strategies for the prevention and treatment of infectious disease. Proposed solutions are outlined by the Centers for Disease Control and Prevention as a multi-pronged approach that include prevention (such as vaccination), improved monitoring, and the development of new treatments. It is this last solution that would encompass the development of new, safe, and effective treatments for infectious diseases.
While most modern antimicrobial drugs have been obtained from microorganisms such as fungi, traditionally, man has used medicinal plants to treat infectious diseases for many centuries. In fact, there are volumes of published scientific data from around the globe describing the antimicrobial activities of plant extracts. A search of the PubMed database (data from 1975 to 2008) shows over 1500 reports in the scientific and medical literature that described the antimicrobial activities of various plant species and their isolated chemical constituents. Furthermore, a search of the NAPRALERT database, a natural products database housed within the University of Illinois at Chicago, shows that of the 58 725 plant species listed in the database, 6350 species had experimental antimicrobial activity, and, of these, nearly 4000 species had ethnomedical data supporting the use of these plants to treat infectious disease. Thus, the investigation of medicinal plants for the development of novel treatments for infectious disease is scientifically rational.
Extracts of many plant species have been tested against literally hundreds of different strains of bacteria. The most common bacterium used in published susceptibility tests include: Escherichia coli, Bacillus subtillis, Chlamydia pneumonia, S. aureus, methicillin-resistant S. aureus (MRSA), Streptococcus pneumoniae, Bacillus cereus, Enterococcus faecalis, Klebsiella pneumoniae, vancomycin-resistant Enterococcus (VRE), Pseudomonas aeruginosa, and Helicobacter pylori. For the purpose of this special supplement to Pharmaceutical Biology we have chosen to focus on medicinal plant extracts with in vitro activity, minimum inhibitory concentrations (MICs) of <100 μg/mL. These concentrations are sufficiently low to be good candidates for further development in animal models or, where appropriate, controlled clinical trials.
The articles published in this special supplement are from around the globe, with special emphasis on medicinal plants used ethnomedically in each country for the treatment of specific infectious diseases. A prime example is the work illustrated in the cover photo of this issue that documents the work, ‘Biological Evaluation of Plants of Laos Used in the Treatment of Tuberculosis in Lao Traditional Medicine’ by Elkington et al. This study investigates plants used historically in Laos for the treatment of tuberculosis, and the authors have correlated these data to determine modern-day usage and evaluated the plant extracts for anti-tuberculosis activity. Similar types of work are ongoing in Nigeria and other countries to develop novel treatments for H. pylori, a Gram-negative bacillus associated with duodenal ulcer disease, peptic ulcer disease, gastric carcinoma, primary gastric B-cell lymphoma, ischemic heart disease, and hyperemesis gravidarum. These papers are also published in this special supplement.
Looking to the future, it is critical that we explore all avenues that may potentially lead to the development of new treatments for infectious diseases. On average, it has been reported that the pharmaceutical industry produces two or three new antibiotics from microorganisms each year. However, over the past 20 years, the number of new antimicrobial drugs in the research and development pipeline has declined. With the advent of secondary infections due to HIV, antibiotic resistance, and new emerging pathogens, any reduction in the development of new therapies for infectious diseases should be considered a serious public health threat. This special supplement was planned to demonstrate that medicinal plants still offer a novel, but relatively untapped, source of potential new therapies for infectious diseases, especially where there are ethnomedical data supporting this use. We hope these contributions will be of value in continuing our quest for superior antimicrobial therapies.