Ethnobotanical approach versus random approach in the search for new bioactive compounds: support of a hypothesis.

CONTEXT: Whether natural product drug discovery programs should rely on wild plants collected "randomly" from the natural environment, or whether they should also include plants collected on the basis of use in traditional medicine remains an open question. OBJECTIVE: This study analyzes whether plants with ethnomedical uses from Vietnam and Laos have a higher hit rate in bioassay testing than plants collected from a national park in Vietnam with the goal of maximizing taxonomic diversity ("random" collection). MATERIALS AND METHODS: All plants were extracted and subjected to bioassay in the same laboratories. Results of assays of plant collections and plant parts (samples) were scored as active or inactive based on whether any extracts had a positive result in a bioassay. Contingency tables were analyzed using χ(2) statistics. RESULTS: Random collections had a higher hit rate than ethnomedical collections, but for samples, ethnomedical plants were more likely to be active. Ethnomedical collections and samples had higher hit rates for tuberculosis, while samples, but not collections, had a higher hit rate for malaria. Little evidence was found to support an advantage for ethnomedical plants in HIV, chemoprevention and cancer bioassays. Plants whose ethnomedical uses directly correlated to a bioassay did not have a significantly higher hit rate than random plants. DISCUSSION: Plants with ethnomedical uses generally had a higher rate of activity in some drug discovery bioassays, but the assays did not directly confirm specific uses. CONCLUSIONS: Ethnomedical uses may contribute to a higher rate of activity in drug discovery screening.

Ethnobotany/ethnopharmacology and mass bioprospecting: issues on intellectual property and benefit-sharing.

Ethnobotany/ethnopharmacology has contributed to the discovery of many important plant-derived drugs. Field explorations to seek and document indigenous/traditional medical knowledge (IMK/TMK), and/or the biodiversity with which the IMK/TMK is attached, and its conversion into a commercialized product is known as bioprospecting or biodiversity prospecting. When performed in a large-scale operation, the effort is referred to as mass bioprospecting. Experiences from the mass bioprospecting efforts undertaken by the United States National Cancer Institute, the National Cooperative Drug Discovery Groups (NCDDG) and the International Cooperative Biodiversity Groups (ICBG) programs demonstrate that mass bioprospecting is a complex process, involving expertise from diverse areas of human endeavors, but central to it is the Memorandum of Agreement (MOA) that recognizes issues on genetic access, prior informed consent, intellectual property and the sharing of benefits that may arise as a result of the effort. Future mass bioprospecting endeavors must take heed of the lessons learned from past and present experiences in the planning for a successful mass bioprospecting venture.

Vaccination against leprosy at Ben San Leprosy Centre, Ho Chi Minh City, Vietnam.

Three vaccines, BCG alone, BCG + 10(7) killed Mycobacterium vaccae and 10(8) killed M. vaccae alone, were studied in children living in close contact with leprosy. In the year before vaccination, 14/446 (3.1%) children had developed leprosy. Among those who were not vaccinated, 9/74 (12.2%) developed the disease in the first 4 years of the study and 5/65 (7.7%) developed the disease in the second 4 years. In comparison with this, among those vaccinated, 20/343 (5.8%) developed leprosy in the first 4 years and 5/323 (1.5%) developed leprosy in the second 4 years. This represents 52.5% protection in the first 4 years and 80.5% in the second 4 years. There were no significant differences in protection afforded by each of the three vaccines but the success of the killed preparation of M. vaccae is an important finding.

A longitudinal study of per cent agalactosyl IgG in tuberculosis patients receiving chemotherapy, with or without immunotherapy.

An increased percentage of circulating IgG molecules that lack galactose from the oligosaccharides on the CH2 domain correlates with disease severity in tuberculosis, rheumatoid arthritis and Crohn's disease. We have recently observed that a single injection of 10(9) autoclaved Mycobacterium vaccae given to tuberculosis patients 7 days after the initiation of chemotherapy causes accelerated clinical improvement, and clearance of bacilli from the sputum. We now show that this immunotherapy also causes rapid loss of agalactosyl IgG, detectable within 14-21 days, whereas chemotherapy alone causes agalactosyl IgG to rise further for up to 2 months. There is simultaneous inhibition of the antibody response to lipoarabinomannan, and transient enhancement of the tuberculin skin-test response. These findings are compatible with a shift from antibody production towards increased cell-mediated immunity. The ideal treatment for tuberculosis would supplement a truncated course of chemotherapy with an immunotherapeutic preparation able to down-regulate the Koch phenomenon and replace it with an efficiently bactericidal mechanism. We tentatively postulate that a fall in per cent agalactosyl IgG [%Gal(0)] in tuberculosis patients may be a marker of such a change.

Enzyme-linked immunosorbent assay using monoclonal antibodies for identification of mycobacteria from early cultures.

A simple enzyme-linked immunosorbent assay (ELISA) for the identification of cultured mycobacteria belonging to the Mycobacterium tuberculosis complex, the Mycobacterium avium complex, and Mycobacterium kansasii has been developed (R. Schöningh, C. P. H. J. Verstijnen, S. Kuijper, and A. H. J. Kolk. J. Clin. Microbiol. 28:708-713, 1990). The test for the routine identification of cultured mycobacteria was introduced in five clinical laboratories located in Tanzania, Thailand, Vietnam, and The Netherlands. The ELISA can be conducted without an ELISA reader since the test can be read visually. The results of identification of 255 strains of the M. tuberculosis complex by microbiological means and by ELISA were compared; the specificity and the sensitivity were 100%. For the M. avium complex, the specificity was 100% and the sensitivity was 64%. All 26 M. kansasii strains tested could be identified as M. kansasii. The ELISA described here proved to be useful in both well- and modestly equipped laboratories and may replace the microbiological method of identification of M. tuberculosis and M. kansasii.

Skin test responsiveness to a series of new tuberculins of children living in three Vietnamese cities.

A skin test survey was conducted among 1035 children aged 7-19 years living in three cities in Vietnam. Fifteen new tuberculins, including leprosin-A, were applied; an induration of 2 mm diameter or more was considered positive. Compared to some other tropical countries, low levels of sensitisation were recorded and remarkable regional differences were found. Positivity to any tuberculins (pooled data) among non-BCG-vaccinated children was significantly lower in Hanoi (13.1%) and HoChiMinh-City [HCMC] (15.5%) than in Nha Trang (25.7%) [p = 0.001 and p = 0.012, respectively]. The proportion of non-vaccinated children responding to Tuberculin ranged from 18.4% in Hanoi to 54.5% in Nha Trang. Leprosin-A elicited a response in 14.9% of the children in Nha Trang, but in very few of those in Hanoi (4.3%) or HCMC (3.0%). Thus, of the three cities studied, significant sensitisation to both M. tuberculosis and M. leprae was demonstrable only in Nha Trang. In Hanoi most of the response was to fast-growing species whilst in HCMC and Nha Trang it was mainly to slow-growing species. These results may account in part for the observed differences in the prevalence of tuberculosis and leprosy between the north and the south of Vietnam.