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ETHNOPHARMACOLOGICAL RELEVANCE: African wormwood (Artemisia afra Jacq. ex Willd.) has been used traditionally in southern Africa to treat illnesses causing fever and was recently shown to possess anti-tuberculosis activity. As tuberculosis is an endemic cause of fever in southern Africa, this suggests that the anti-tubercular activity of A. afra may have contributed to its traditional medicinal use. AIM OF THE STUDY: Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is a deadly and debilitating disease globally affecting millions annually. Emerging drug-resistant Mtb strains endanger the efficacy of the current therapies employed to treat tuberculosis; therefore, there is an urgent need to develop novel drugs to combat this disease. Given the reported activity of A. afra against Mtb, we sought to determine the mechanisms by which A. afra inhibits and kills this bacterium. MATERIALS AND METHODS: We used transcriptomics to investigate the impact of Artemisia spp. extracts on Mtb physiology. We then used chromatographic fractionation and biochemometric analyses to identify a bioactive fractions of A. afra extracts and identify an active compound. RESULTS: Transcriptomic analysis revealed that A. afra exerts different effects on Mtb compared to A. annua or artemisinin, suggesting that A. afra possesses other phytochemicals with unique modes of action. A biochemometric study of A. afra resulted in the isolation of an O-methylflavone (1), 5-hydroxy-7-methoxy-2-(4-methoxyphenyl)chromen-4-one, which displayed considerable activity against Mtb strain mc26230 in both log phase growth and metabolically downshifted hypoxic cultures. CONCLUSIONS: The present study demonstrated that an O-methylflavone constituent of Artemisia afra explains part of the activity of this plant against Mtb. This result contributes to a mechanistic understanding of the reported anti-tubercular activity of A. afra and highlights the need for further study of this traditional medicinal plant and its active compounds.

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Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is a deadly and debilitating disease globally affecting millions annually. Emerging drug-resistant Mtb strains endanger the efficacy of the current combination therapies employed to treat tuberculosis; therefore, there is an urgent need to develop novel drugs to combat this disease. Artemisia afra is used traditionally in southern Africa to treat malaria and recently has shown anti tuberculosis activity. This genus synthesizes a prodigious number of phytochemicals, many of which have demonstrated human health effects. Transcriptomic analysis revealed that A. afra exerts different effects on Mtb compared to A. annua or the well-known antimalarial artemisinin, suggesting other phytochemicals present in A. afra with unique modes of action. A biochemometric study of A. afra resulted in the isolation of a methoxylated flavone (1), which displayed considerable activity against Mtb strain mc26230. Compound 1 had an MIC of 312.5 µg/mL and yielded no viable colonies after 6 days of treatment. In addition, 1 was effective in killing hypoxic Mtb cultures, with no viable cultures after 2 days of treatment. This suggested that A. afra is a source of potentially powerful anti-Mtb phytochemicals with novel mechanisms of action.

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OBJECTIVE: To identify factors influencing pharmacists' decisions about selling syringes to injection drug users (IDUs). DESIGN: Audiotaped interviews. SETTING: Denver, Colorado. PARTICIPANTS: Thirty-two pharmacists at 24 pharmacies. INTERVENTION: One-hour semistructured interviews. MAIN OUTCOME MEASURES: Practices regarding syringe sales to IDUs and factors influencing the practices. RESULTS: Of the 32 pharmacists interviewed, 16 indicated that they sold syringes to all customers ("pro-sell"), 11 refused to sell unless shown proof of diabetic status ("no-sell"), and 5 were "undecided." Several factors influenced the decision to sell. A perceived conflict between prevention of disease and prevention of drug abuse most clearly distinguished the three categories, with pro-sell pharmacists more likely than others to prioritize disease prevention and believe that syringe sales would not increase drug abuse. Business concerns, such as the effect of the presence of IDUs on other customers and the possibility of discarded syringes around the store, were especially prevalent among no-sell and undecided pharmacists. Seventeen pharmacists did not know about Colorado laws governing syringe sales. Four no-sell pharmacists used the laws to justify their decision not to sell, and two undecided pharmacists said they used the law when they did not want to sell syringes to IDU. All pharmacists supported syringe exchange programs. CONCLUSION: One-half of the pharmacists sold syringes to IDUs, and several more indicated that they would do so if certain concerns were addressed. These data suggest that improved syringe disposal options, continuing education programs, and clarification of existing laws and regulations would encourage more pharmacists in Denver to sell syringes to IDUs.

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OBJECTIVE: To determine the availability of syringes for injection drug users (IDUs) from pharmacies in Denver. DESIGN: Single-group, uncontrolled, noncomparative study. SETTING: Denver, Colorado. PATIENTS OR OTHER PARTICIPANTS: 23 randomly selected pharmacies in the Denver metropolitan area and 3 additional pharmacies located near drug-buying locations. INTERVENTION: Attempt by eight trained IDU "research assistants" to purchase packages of 10 U-100 insulin syringes without a prescription from pharmacies. MAIN OUTCOME MEASURES: Successful purchase of syringes; reasons for refusal. RESULTS: Of 26 pharmacies, 4 reported not stocking syringes, 3 did not sell syringes to any research assistants, 10 sold to some research assistants but not to others, and 9 sold to all research assistants. Of 206 purchase attempts, 54% were successful. In 37.9% of 95 refusals, the pharmacist reported that syringes were not sold at the store, and in 28.4% the pharmacist refused to sell because the research assistant did not produce diabetic identification or answer insulin-related questions. No differences in pharmacy response were found with respect to the racial or ethnic characteristics of the research assistant. Price varied substantially within and among stores. No pharmacies that sold syringes to research assistants were open 24 hours per day. CONCLUSION: While IDUs who live near a pharmacy that regularly sells syringes and IDUs with a convincing diabetes story may have adequate access to syringes, others face inconsistent availability. Price fluctuations and limited hours of those pharmacies that sell syringes may be additional barriers to access to sterile syringes for IDUs in Denver.

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