Towards Improved Management of Tuberculous Bloodstream Infections: Pharmacokinetic Considerations with Suggestions for Better Treatment Outcomes.

Mycobacterium tuberculosis is the leading cause of sepsis among HIV-infected adults, yet effective treatment remains a challenge. Efficacy of antituberculous drugs is optimized by high Area Under Curve to Minimum Inhibitory Concentration (AUC/MIC) ratios, suggesting that both the drug concentration at the disease site and time above MIC are critical to treatment outcomes. We elaborate on sepsis pathophysiology and show how it adversely affects antituberculous drug kinetics. Expanding distribution volumes secondary to an increased vascular permeability prevents the attainment of target Cmax concentrations for nearly all drugs. Furthermore, sepsis-induced metabolic acidosis promotes protonation, which increases renal clearance of basic drugs such as isoniazid and ethambutol, and hence AUCs are substantially reduced. Compared with the treatment of non-sepsis TB disease, these distorted kinetics underlie the poor treatment outcomes observed with bloodstream infections. In addition to aggressive hemodynamic management, an increase in both the dose and frequency of drug administration are warranted, at least in the early phase of treatment.

Training the next generation of Africa's doctors: why medical schools should embrace the team-based learning pedagogy.

BACKGROUND: As far back as 1995, the Cape Town Declaration on training Africa's future doctor recognized the need for medical schools to adopt active-learning strategies in order to nurture holistic development of the doctor. However, medical education in Africa remains largely stuck with traditional pedagogies that emphasize the 'hard skills' such as knowledge and clinical acumen while doing little to develop 'soft skills' such as effective communication, teamwork, critical thinking or life-long learning skills. By reviewing literature on Africa's epidemiologic and demographic transitions, we establish the need for increasing the output of well-trained doctors in order to match the continent's complex current and future healthcare needs. Challenges that bedevil African medical education such as outdated curricula, limited educational infrastructure and chronic resource constraints are presented and discussed. Furthermore, increased student enrollments, a trend observed at many schools, coupled with chronic faculty shortages have inadvertently presented specific barriers against the success of small-group active-learning strategies such as Problem-Based and Case-Based Learning. We argue that Team-Based Learning (TBL) offers a robust alternative for delivering holistic medical education in the current setting. TBL is instructor-driven and embodies key attributes that foster development of both 'hard' and 'soft' skills. We elaborate on advantages that TBL is likely to bring to the African medical education landscape, including increased learner enthusiasm and creativity, accountability, peer mentorship, deep learning and better knowledge retention. As with all new pedagogical methods, challenges anticipated during initial implementation of TBL are discussed followed by the limited pilot experiences with TBL in Africa. CONCLUSION: For its ability to enable a student-centered, active learning experience delivered at minimum cost, we encourage individual instructors and African medical schools at large, to adopt TBL as a complementary strategy towards realizing the goal of training Africa's fit-for-purpose doctor.

Burden of Placental Malaria among Pregnant Women Who Use or Do Not Use Intermittent Preventive Treatment at Mulago Hospital, Kampala.

Intermittent preventive treatment of malaria in pregnancy with sulphadoxine-pyrimethamine (SP-IPTp) is widely used to reduce the incidence of adverse pregnancy outcomes. As a monitor for continued effectiveness of this intervention amidst SP resistance, we aimed to assess malaria burden among pregnant women who use or do not use SP-IPTp. In a descriptive cohort study at Mulago Hospital, Kampala, 87 women who received two supervised doses of SP-IPTp were followed up until delivery. Controls were pregnant women presenting in early labour without history of SP-IPTp. Histopathological investigation for placental malaria (PM) was performed using the Bulmer classification criterion. Thirty-eight of the 87 women returned for delivery and 33 placentas were successfully collected and processed along with 33 placentas from SP nonusers. Overall, 12% (4/33) of the users had evidence of PM compared to 48% (16/33) of nonusers. Among nonusers, 17/33, 8/33, 2/33, and 6/33 had no placental infection, active infection, active-chronic infection, and past-chronic infection, respectively. Among users, respective proportions were 29/33, 2/33, 0/33, and 2/33. No difference in birth weights was apparent between the two groups, probably due to a higher proportion of infections occurring later in pregnancy. Histological evidence here suggests that SP continues to offer substantial benefit as IPTp.

Chewing-stick practices using plants with anti-streptococcal activity in a ugandan rural community.

BACKGROUND: The high dental disease burden in developing countries has created a need to explore and develop cheap and accessible methods of dental disease prevention. Traditional toothbrushes (chewing-sticks) prepared from specific plants have been used for dental hygiene for generations. When properly used, chewing-sticks may be as effective as synthetic toothbrushes. This study set out to describe traditional chewing-stick practices in a Ugandan rural community, and evaluate the antibacterial activity of two most commonly used plants. METHODS: Interviews were done to identify chewing-stick plants and obtain socio-cultural information relating to the practice in two villages in rural Uganda. Field walks were done to pick and voucher the plants, for taxonomical identification and storage. For the two most reported plants, aqueous extracts were prepared and tested for antibacterial activity against Streptococcus mutans using the agar-well diffusion method. RESULTS: Of the 21 key informants interviewed, all were using or had used chewing-sticks in the past. A total of eight plants were identified as sources of chewing-sticks, with Rhus vulgaris and Lantana trifolia most commonly mentioned. Chewing-sticks were preferred over synthetic tooth brushes because they were less likely to traumatize the gums. Their use has been limited of recent due to scarcity of some plants. R. vulgaris and L. trifolia aqueous extracts showed antibacterial activity against S. mutans with mean diameters of inhibition of 24.33 ± 0.58 and 14.17 ± 0.29 mm on Blood agar respectively, compared to benzyl penicillin control 30.67 ± 0.29 mm. CONCLUSION: R. vulgaris and L. trifolia are the most common sources of chewing-sticks for cleaning teeth in this community. The plants contain compounds that are active against S. mutans. These plants merit further studies as they are possible sources of cheap dental health care for the rural poor.