Registration and local production of essential medicines in Uganda

Universal access to high quality essential medicines is critical to sustainable development (SDG 3.8). However low- and middle-income countries struggle to ensure access to all medicines on their national essential medicines lists (EML). Market registration is the first step in determining both access and availability yet the extent to which essential medicines are registered for use at country level is not known. Companies apply for a marketing authorisation, however low price or lack of a market is a disincentive. Local production has been promoted to ensure availability of essential medicines but research in this area is also limited.; The study took place between 2011 and 2015. We systematically examined the registration status of medicines and vaccines listed in the Ugandan 2012 EML and conducted 20 interviews with regulators, ministry of health representatives, donors, and pharmaceutical producers and analysed quality assurance issues affecting registration, procurement, and local production of medicines in Uganda. In 2017 we conducted a further three interviews to clarify issues around non-registration of essential medicines highlighted by our analysis.; Of the 566 essential medicines and vaccines nearly half (49%; 275/566) had no registered product in 2012. Of the 3130 registered products, just over a quarter (28%; 880/3130) were listed on the EML. Six local producers had registered 138 products of which 40 corresponded to 32 unique essential medicines. Interviews highlighted alternative routes to availability other than registration. Local producers faced considerable barriers to achieving international quality standards required for international procurement of medicines for the domestic market.; Monitoring and audit of the registration of essential and non-essential medicines should be a priority nationally and, regionally through harmonisation of registration requirements in the East African Community. National and regional manufacturing plans should consider local production of unregistered essential medicines

Sublingual misoprostol versus intramuscular oxytocin for prevention of postpartum hemorrhage in Uganda: a double-blind randomized non-inferiority trial

Background: Postpartum hemorrhage (PPH) is a leading cause of maternal death in sub-Saharan Africa. Although the World Health Organization recommends use of oxytocin for prevention of PPH, misoprostol use is increasingly common owing to advantages in shelf life and potential for sublingual administration. There is a lack of data about the comparative efficacy of oxytocin and sublingual misoprostol, particularly at the recommended dose of 600 mu g, for prevention of PPH during active management of labor. Methods and Findings: We performed a double-blind, double-dummy randomized controlled non-inferiority trial between 23 September 2012 and 9 September 2013 at Mbarara Regional Referral Hospital in Uganda. We randomized 1,140 women to receive 600 mu g of misoprostol sublingually or 10 IU of oxytocin intramuscularly, along with matching placebos for the treatment they did not receive. Our primary outcome of interest was PPH, defined as measured blood loss >= 500 ml within 24 h of delivery. Secondary outcomes included measured blood loss >= 1,000 ml; mean measured blood loss at 1, 2, and 24 h after delivery; death; requirement for blood transfusion; hemoglobin changes; and use of additional uterotonics. At 24 h postpartum, primary PPH occurred in 163 (28.6%) participants in the misoprostol group and 99 (17.4%) participants in the oxytocin group (relative risk [RR] 1.64, 95% CI 1.32 to 2.05, p<0.001; absolute risk difference 11.2%, 95% CI 6.44 to 16.1). Severe PPH occurred in 20 (3.6%) and 15 (2.7%) participants in the misoprostol and oxytocin groups, respectively (RR 1.33, 95% CI 0.69 to 2.58, p = 0.391; absolute risk difference 0.9%, 95% CI -1.12 to 2.88). Mean measured blood loss was 341.5 ml (standard deviation [SD] 206.2) and 304.2 ml (SD 190.8, p = 0.002) at 2 h and 484.7 ml (SD 213.3) and 432.8 ml (SD 203.5, p<0.001) at 24 h in the misoprostol and oxytocin groups, respectively. There were no significant differences between the two groups in any other secondary outcomes. Women in the misoprostol group more commonly experienced shivering (RR 1.91, 95% CI 1.65 to 2.21, p<0.001) and fevers (RR 5.20, 95% CI 3.15 to 7.21, p = 0.005). This study was conducted at a regional referral hospital with capacity for emergency surgery and blood transfusion. High-risk women were excluded from participation. Conclusions: Misoprostol 600 mu g is inferior to oxytocin 10 IU for prevention of primary PPH in active management of labor. These data support use of oxytocin in settings where it is available. While not powered to do so, the study found no significant differences in rate of severe PPH, need for blood transfusion, postpartum hemoglobin, change in hemoglobin, or use of additional uterotonics between study groups. Further research should focus on clarifying whether and in which sub-populations use of oxytocin would be preferred over sublingual misoprostol

The availability of six tracer medicines in private medicine outlets in Uganda

Abstract Objectives: Many low income countries struggle to provide safe and effective medicines due to poor public health care infrastructure, budgetary constraints, and lack of human resource capacity. Private sector pharmacies and drug shops are used by a majority of the population as an alternative to public pharmacies. This study looks at the availability of six essential medicines in private drug outlets across Uganda. Methods: A standardised medicines availability survey developed by the World Health Organization and Health Action International was adapted for use in this project to collect availability data for six tracer medicines in 126 private medicine outlets across four districts in Uganda from September 2011 to October 2012. Results: Artemisinin-based combination treatments and metformin were the most commonly found medicines in the private medicine outlets surveyed. Ninty-nine percent of all outlets carried artemisinin-based combinations while 93% of pharmacies and 53% of drug shops stocked metformin. Oxytocin was found in one third of outlets surveyed. Fluoxetine was in 70% of pharmacies yet was not found in any drug shops. Rifampicin and lamivudine were found infrequently in outlets across all districts; 10% and 2%, respectively. Not all brands found in surveyed outlets were listed on the Ugandan National Drug Register. In particular, five unlisted brands of rifampicin were found in private medicine outlets. Conclusions: The regulatory process should be improved through the enforcement of outlet licensing and medicine registration. Additional studies to elucidate the reasons behind the use of private medicine outlets over the public sector would assist the government in implementing interventions to increase use of public sector medicine outlets

Pharmacognostic, antiplasmodial and antipyretic evaluation of the aqueous extract of Vernonia amygdalina leaf

ABSTRACT The impeding safety challenges to the use of herbs have made qualitative and quantitative evaluation of herbal preparations a necessity. This study was aimed at evaluating the pharmacognostic and pharmacological properties of V. amygdalina leaf. Methods used include standard procedure for macroscopic and microscopic examinations; ash and extractive values determination; and quantitative evaluation of phytochemicals of the leaf aqueous extract. 4-day antiplasmodial suppression test using mice and antipyretic evaluation in rats induced pyrexia by i.p administration of 15% and dose induced body temperature decrease, were significant (P ≤ 0.05) for all the 3 dose levels of the extract used. Study agrees with folkloric use of the leaf extract in malaria fever but suggests substantial antipyretic property of the leaf

Measuring Post-Partum Haemorrhage in Low-Resource Settings: The Diagnostic Validity of Weighed Blood Loss versus Quantitative Changes in Hemoglobin

Background: Accurate estimation of blood loss is central to prompt diagnosis and management of post-partum hemorrhage (PPH), which remains a leading cause of maternal mortality in low-resource countries. In such settings, blood loss is often estimated visually and subjectively by attending health workers, due to inconsistent availability of laboratory infrastructure. We evaluated the diagnostic accuracy of weighed blood loss (WBL) versus changes in peri-partum hemoglobin to detect PPH. Methods: Data from this analysis were collected as part of a randomized controlled trial comparing oxytocin with misoprostol for PPH (NCT01866241). Blood samples for complete blood count were drawn on admission and again prior to hospital discharge or before blood transfusion. During delivery, women were placed on drapes and had pre-weighed sanitary towels placed around their perineum. Blood was then drained into a calibrated container and the sanitary towels were added to estimate WBL, where each gram of blood was estimated as a milliliter. Sensitivity, specificity, negative and positive predictive values (PPVs) were calculated at various blood volume loss and time combinations, and we fit receiver-operator curves using blood loss at 1, 2, and 24 hours compared to a reference standard of haemoglobin decrease of >10%. Results: A total of 1,140 women were enrolled in the study, of whom 258 (22.6%) developed PPH, defined as a haemoglobin drop >10%, and 262 (23.0%) had WBL ≥500mL. WBL generally had a poor sensitivity for detection of PPH (85%) in high prevalence settings when WBL exceeds 750mL. Conclusion: WBL has poor sensitivity but high specificity compared to laboratory-based methods of PPH diagnosis. These characteristics correspond to a high PPV in areas with high PPH prevalence. Although WBL is not useful for excluding PPH, this low-cost, simple and reproducible method is promising as a reasonable method to identify significant PPH in such settings where quantifiable red cell indices are unavailable

Provision of family planning vouchers and early initiation of postpartum contraceptive use among women living with HIV in southwestern Uganda: A randomized controlled trial.

BackgroundUnwanted pregnancies remain a burden for women living with HIV (WLWH). Family planning prevents unplanned pregnancies while promoting longer birth intervals, key strategies to eliminate perinatal transmission of HIV and promote maternal and child health. We evaluated the effect of a family planning voucher, inclusive of immediate postpartum counseling, on uptake, early initiation, and continuation of modern contraceptive methods among recently postpartum WLWH delivering at a publicly funded regional referral hospital in rural, southwestern Uganda.Methods and findingsWe performed a randomized controlled trial between October, 2016 and June, 2018 at a referral hospital in southwestern Uganda. This interim analysis includes adult WLWH randomized and enrolled equally to receive a family planning voucher or standard of care (control). Enrolled postpartum WLWH completed an interviewer-administered questionnaire at enrollment and 6 months postpartum. Our primary outcome of interest for this analysis is initiation of a modern family planning method within 8 weeks postpartum. Secondary outcomes included family planning initiation at 12, 14, 16, and 20 weeks postpartum, family planning discontinuation and/or change, pregnancy incidence, and mean time without contraception. The trial was registered with clinicaltrials.gov (NCT02964169). At enrollment, half of the women in both the voucher (N = 87, 55%) and control (N = 86, 54%) groups wanted to have a child in 2 years postpartum. Over 80% of referent pregnancies in the voucher (N = 136, 86%) and control (N = 128, 81%) groups were planned. All women were accessing ART. The mean CD4 count was 396 cells/mm3 (SD = 61) for those enrolled in the control group versus 393 cells/mm3 (SD = 64) in the family planning voucher group. By 8 weeks postpartum, family planning was initiated in 144 (91%) participants in the voucher group and 83 (52%) participants in the control group (odds ratio [OR] 9.42; CI 4.67-13.97, P ConclusionThese findings indicate that a well-structured, time-bound family planning voucher program appeared to increase early postpartum contraceptive uptake and continuation in a setting in which users are faced with financial, knowledge, and structural barriers to contraceptive services. Further work should clarify the role of vouchers in empowering WLWH to avoid unintended pregnancies over time.Trial registrationClinicalTrials.gov NCT02964169

Phytochemical and Antidiabetic Evaluation of the Methanolic Stem Bark Extract of Spathodea campanulata (P. Beauv.) Bignoniaceae

ABSTRACT Background: Spathodea campanulata (P. Beauv.) Bignoniaceae extract (SCE) is one of many herbal medicines used widely in Ugandan traditional medicine for various ailments. Generally most of these herbal medicines are yet to be standardized or have their phytochemical content characterized. Method: This study identified the secondary metabolites in the stem bark methanolic extract and quantified them. The same extract was subjected to serial solvent fractionation, TLC characterization and antidiabetic testing

Evaluation of the Acute and Subactue chronic Toxicities of the Methanolic Stem Bark Extract of Spathodea campanulata (P.Beauv.) Bignoniaceae

status: publishe