Pharmacokinetics of the nonnucleoside reverse transcriptase inhibitor efavirenz among HIV-infected Ugandans.

BACKGROUND: Pharmacokinetic variability of the nonnucleoside reverse transcriptase inhibitor efavirenz has been documented, and high variation in trough concentrations or clearance has been found to be a risk for virological failure. Africans population exhibits greater variability in efavirenz concentrations than other ethnic groups, and so a better understanding of the pharmacokinetics of the drug is needed in this population. This study characterized efavirenz pharmacokinetics in HIV-infected Ugandans. METHODS: Efavirenz plasma concentrations were obtained for 66 HIV-infected Ugandans initiating efavirenz- based regimens, with blood samples collected at eight time-points over 24 h on day 1 of treatment, and at a further eight time-points on day 14. Noncompartmental analysis was used to describe the pharmacokinetics of efavirenz. RESULTS: The mean steady-state minimum plasma concentration (C(min) ) of efavirenz was 2.9 µg/mL, the mean area under the curve (AUC) was 278.5 h µg/mL, and mean efavirenz clearance was 7.4 L/h. Although overall mean clearance did not change over the 2 weeks, 41.9% of participants showed an average 95.8% increase in clearance. On day 14, the maximum concentration (C(max) ) of efavirenz was >4 µg/mL in 96.6% of participants, while C(min) was <1 µg/mL in only 4.5%. Overall, 69% of participants experienced adverse central nervous system (CNS) symptoms attributable to efavirenz during the 2-week period, and 95% of these participants were found to have efavirenz plasma concentrations >4 µg/mL, although only half maintained a high concentration until at least 8 h after dosing. CONCLUSION: The findings of this study show that HIV-infected patients on efavirenz may exhibit autoinduction to various extents, and this needs to be taken into consideration in the clinical management of individual patients. Efavirenz CNS toxicity during the initial phase of treatment may be related to C(max) , regardless of the sampling time.

The efficacy of the crude root bark extracts of Erythrina abyssinica on rifampicin resistant Mycobacterium tuberculosis.

INTRODUCTION: Tuberculosis (TB) is one of the leading causes of morbidity and mortality with a global mortality rate at two million deaths per year while one third of the world's population is infected with the TB bacillus. OBJECTIVE: To determine the efficacy of the crude extracts of Erythrina abyssinica root bark on rifampicin-resistant TB. METHODS: Crude extracts of root bark of Erythrina abyssinica, were screened against three strains of Mycobacterium tuberculosis including rifampicin-resistant TMC-331. Susceptibility tests used the disc diffusion method and were done on solid Middle brook 7H10, while the Minimum Inhibitory concentration (MICs) and minimum bactericidal concentration (MBCs) were determined by the Microtitre plate method using Middle brook 7H9 broth. RESULTS: The total crude methanol extract showed activity against all the three strains of mycobacterium used, at 50mg/ml and diameters of zones of inhibition of up to 26 mm. Erythrina abyssinica total crude methanol extract showed the highest activity on the pan sensitive strain H37Rv (0.39±0.0 mg/ml) and the rifampicin resistant strain (TMC-331) (2.35±1.11 mg/ ml) and was also active on Mycobacterium avium (0.39±0.mg/ml. The values for isoniazid were 0.25µg/ml and 9.38µg/ml for H37Rv and TMC-331 respectively, while for rifampicin the MIC value was 0.25µg/ml for H37Rv but it was not active on TMC-331. Acute toxicity test gave an LD50 of 776.2mg/kg body weight while the phytochemical analysis showed the presence of alkaloids, tannins and flavones. CONCLUSION: The conclusion from the study was that Erythrina abbyssinica has antimycobacterial activity and reasonable safety that merits further research.

The prevalence and severity of mental illnesses handled by traditional healers in two districts in Uganda

Background: Little is known about the prevalence and severity of DSM-IV mental disorders treated by traditional healers in Uganda. Objective: To describe the prevalence and severity of DSM-IV disorders handled by traditional healers in Jinja and Iganga districts; Eastern Uganda. Method: Between January and March 2008; Face-to-Face Interviews were conducted with 400 patients attending traditional healers' shrines for mental health problems; using Self Rating Questionnaire 25 (SRQ-25) for screening; the Mini International Neuropsychiatric Interview (MINI-Plus) for specific DSM-IV diagnosis and the Global Assessment of Functioning (GAF) for severity of illness. Descriptive data analysis and frequency estimates were performed using SPSS version 15.0 for Windows. Pearson's chisquare tests and odds ratios were used to explore the relationship between severity and combined use of biomedical services and traditional healing. Results: Of 387 respondents; 60.2had diagnosable current mental illness and 16.3had had one disorder in their lifetime. Of the diagnosable current mental illnesses; 29.7were Psychosis; 5.4Major depressive episode; 5.6Anxiety disorders; 3.6mixed Anxiety-Depression; and 3.9Suicidality. In terms of severity; 37.7of the current mental illnesses were severe; 35.1moderate and 13.2mild. Patients with moderate to severe symptoms were more likely to use both biomedical services and traditional healers. Conclusion: These findings suggest that a considerable number of patients with DSM-IV diagnosable mental disorders attend traditional healing shrines; the majority had moderate to severe symptoms. Mental health professionals therefore need to come up with ways to co-operate with traditional healers; e.g. as officially designated Traditional Mental Attendants (TMA); for the benefit of their patients

In vitro interactions of Aspilia africana (Pers.) C.D. Adams, a traditional antimalarial medicinal plant, with artemisinin against Plasmodium falciparum.

Traditional antimalarial medicinal preparations are widely used concurrently with antimalarial drugs in malaria endemic areas. The plant Aspilia africana (Pers.) C.D. Adams is commonly used for traditional treatment of malaria symptoms in East and Central Africa. An in vitro study of interactions between an extract from this plant with artemisinin against two strains of Plasmodium falciparum showed an antagonist relationship against both the chloroquine-sensitive D10 and the chloroquine- and sulphonamide-resistant K1 strains of Plasmodium falciparum. The extract reduced accumulation of radiolabelled dihydroartemisinin ((3)H-DHA) by erythrocytes infected with the chloroquine- and sulphonamide-resistant K1 strain of Plasmodium falciparum while it increased its accumulation by erythrocytes infected with the chloroquine-sensitive D10 strain. These results suggest complex interactions between the antimalarial medicinal plant and artemisinin. This study also proposes an in vitro approach to investigating interactions between antimalarial drugs and traditional medicines.

The in vitro and in vivo antimalarial activity of Cardiospermum halicacabum L. and Momordica foetida Schumch. Et Thonn.

Two plants Cardiospermum halicacabum L. and Momordica foetida Schumch. Et Thonn traditionally used to treat symptoms of malaria in parts of East and Central Africa were screened for in vitro and in vivo antimalarial activity. Using the nitro tetrazolium blue-based parasite lactate dehydrogenase assay as used by [Makler, M.T., Ries, J.M., Williams, J.A., Bancroft, J.E., Piper, R.C., Gibbins, B.L., Hinrichs, D.J., 1993. Parasite lactate dehydrogenase as an assay for Plasmodium falciparum drug sensitivity. American Journal of Tropical Medicine and Hygiene 48, 739-741], water extracts from the two plants were found to have weak in vitro antiplasmodial activity with 50% inhibitory concentrations (IC50s) greater than 28.00 microg/ml. In vivo studies of water extracts from the two plants showed that Momordica foetida given orally in the dose range 10, 100, 200 and 500 mg/kg twice daily prolonged survival of Plasmodium berghei (Anka) infected mice from 7.0+/-1.8 to 17.9+/-1.8 days. The water extract of Cardiospermum halicacabum L was toxic to mice, none surviving beyond day 4 of oral administration, with no evidence of protection against Plasmodium berghei malaria. The study emphasizes the discrepancy that might be found between in vitro and in vivo testing of plant-derived antimalarial extracts and the need to consider in vitro antiplasmodial data with this in mind. Further studies on Momordica foetida as a source of an antimalarial remedy are indicated on the basis of these results.

Impact of an educational intervention to improve prescribing by private physicians in Uganda.

INTRODUCTION: Private physicians in urban Uganda treat a large percentage of common adult illnesses. Improving their prescribing would not only encourage more rational drug use, but also reduce costs to patients. Interventions to improve drug use are generally more successful when face-to-face educational methods are included. OBJECTIVES: To determine the effectiveness of a face-to-face educational intervention on the treatment of acute respiratory infections (ARI), malaria, and non-dysenteric diarrhoea by private physicians in three urban areas of Uganda. METHODS: The study used an intervention with comparison group design to evaluate the impact of the educational intervention. A total of 108 private physicians was divided into intervention (n = 30) and control (n = 78) groups. Surrogate patients, trained to simulate presenting symptoms and signs of the target conditions, were used to collect data on the medical practices and prescribing behaviours of the physicians. Intervention physicians were invited to a one-day interactive educational seminar facilitated by local opinion leaders that covered principles of rational drug use and the National Standard Treatment Guidelines for treating the target conditions. Physicians were also provided with data about baseline practices. RESULTS: Baseline data indicated high rates of inappropriate treatment practices by both intervention and control groups. There was nearly universal antibiotic use for ARI (over 90%), high rates of injections recommended for malaria (over 30%), and high rates of polypharmacy (over thee drugs per patient). After the intervention, some significant improvements in key practices were observed in the intervention group. Compared to control physicians, antibiotic prescribing for ARI decreased by 23% in the intervention group, use of combination products for malaria declined by 28%, there were trends towards better adherence to guidelines for ARI and malaria, and marginal decreases in drug costs. However, the overall impacts of the intervention were limited, especially on quality indicators concerning history taking, adequate examination, and advice to patients. CONCLUSION: The face-to-face educational intervention resulted in some small improvements in key prescribing practices of private physicians. However, an intervention that involved repeated contacts with prescribers and which addressed economic considerations would be needed to obtain larger improvements. Private physicians need to be sensitized to and encouraged to use the National Standard Treatment Guidelines, and attempts to improve their prescribing should be supported by community education.

A comparison of prescribing practices between public and private sector physicians in Uganda.

INTRODUCTION: Previous studies in the public sector in Uganda have demonstrated major prescribing problems due to polypharmacy and irrational use of antibiotics and injections. Little is known about prescribing in the private sector although there is little government regulation influencing practice in this sector. The introduction of policies such as the Uganda National Standard Treatment Guidelines (UNSTG) was expected to improve prescribing practices in the public and private sectors. This paper measures appropriateness of prescribing practices in the public and private sectors in Uganda for the treatment of Acute Respiratory Infections (ARI) and malaria in adult patients. DESIGN AND SAMPLING: We combined a prospective survey of treatment for simulated patients presenting with symptoms of malaria and ARI in 119 randomly selected private clinics and a retrospective survey of 600 prescription records for malaria and ARI (300 for each condition) randomly selected from 10 public health units in the Kampala, Masaka, and Jinja urban areas. OUTCOME MEASURES: Percentage of drug appropriately prescribed in each condition, % injection prescription, percentage antibiotic prescription, average number of drugs per case, average standardized cost per prescription, distribution of types of drugs prescribed. RESULTS: The overall appropriateness of prescribing for ARI and malaria was poor in both public and private sectors. Treatment of malaria was significantly less appropriate in the public sector compared to the private sector (14% vs. 27%, p = 0.002), with injectable chloroquine much more commonly prescribed. Prescribing of antibiotics for ARI was nearly universal in both sectors, with some prescriptions containing up to three antibiotics; newer, more expensive antibiotics were more commonly prescribed in the private sector. Polypharmacy and unnecessary prescribing of vitamins were common in both conditions and both sectors. CONCLUSIONS: Prescribing for adult malaria and ARI by both private and public practitioners did not conform to the UNSTGs. Although practitioners were largely the same in both sectors, prescribing practices often differed dramatically. The extent of inappropriate prescribing in both sectors calls for in-depth investigation of the system factors and motivations that underlie problem practices, and the development of interventions that target these causative factors.