Cost and availability of selected medicines after implementation of increased import verification fees.

BACKGROUND: Uganda imports approximately 90% of its medicines, with about 60% being distributed by the private sector. To discourage importation and promote local production of 37 selected locally manufactured medicines, the Ugandan government through the Ministry of Health in 2017 increased the import verification fees from 2 to 12%. The increase in verification fees ultimately affects cost and availability of these medicines. This study aimed to assess the cost and availability of the selected essential medicines after the 12% increase in verification fees in Uganda. METHODS: A cross sectional study among 328 wholesale and retail pharmacies and seven key informant interviews was conducted using a pretested data collection checklist and in-depth interview guide from February to September 2021 in Uganda. Data on the availability and prices of the medicines before (2017) and after (2020) the increase in verification fees was collected. Paired sample T-Test was used to test if there is a significant difference in prices before and after the 12% increase in verification fees. RESULTS: Mean availability of imported medicines was higher (54.8%, CI: 49.3-60.4) than the locally produced medicines (37.1%, CI: 31.9-42.7) except for locally manufactured parenteral preparations (54.6.%, CI: 49.1-60.1). Availability of locally produced medicines was mainly low (45%) while the imported medicines were fairly high (74%). Most commonly available locally manufactured medicines were Surgical spirit (89.9%), ORS (86%), Dextrose 5% solution (74.4%), Paracetamol 500 mg Tablets (73.8%) and Sodium Chloride 0.9% solution (72.9%). Most commonly available imported medicines were; Omeprazole 20 mg (94.2%), Amoxicillin Trihydrate 125 mg/5 ml (92.4%), Ciprofloxacin 500 mg (91.4%), Paracetamol Suspension 120 mg/5 ml (91.5%) and Metronidazole 200 mg Tablets (88.1%). Increase in lowest-priced local and imported medicines was significant for 10 (23.8%) and 7 (15.9%) of the medicines respectively. The median prices of imported medicines were generally higher than locally produced medicines. The median unit prices of 12 (28.6%) locally produced medicines and 20 (47.6%) imported medicines were higher than the international median unit prices. CONCLUSIONS: The overall availability of imported medicines was still higher than the local medicines. The median prices of local and imported medicines generally increased or remained the same after the introduction of import verification fees. There is a need for price controls and transparency in the private sector.

Antimicrobial consumption surveillance in Uganda: Results from an analysis of national import data for the human health sector, 2018-2021.

BACKGROUND: The surveillance of antimicrobial consumption (AMC) is critical to developing appropriate antimicrobial stewardship interventions. It is a key component of World Health Organization's (WHO) Global Action Plan on Antimicrobial Resistance and the Uganda Antimicrobial Resistance National Action Plan 2018-2023. Our study's objective was to determine the national consumption of all antimicrobials. METHODS: Data on all imported antimicrobials were retrieved from paper-based records and entered in the web-based National Drug Authority (NDA) management information system from 2021. The import data for the year is a proxy for nationwide consumption because they account for 95% of all medical products. The NDA authorizes all imports to the country regardless of final distribution in the supply chain. The data were analyzed in accordance with WHO Anatomical Therapeutic Chemical codes and defined daily dose (DDD) methodology. We also retrieved consumption data for 2018, 2019, and 2020 that were previously submitted by Uganda to WHO's Global Antimicrobial Resistance and Use Surveillance System. RESULTS: In 2021, the average DDD per 1000 inhabitants was 29.02 for all antimicrobials; 80.7% of antimicrobials consumed were oral. Penicillins (27.6%) were the most consumed antimicrobial class, followed by sulfonamides and trimethoprim (15.5%). Based on WHO's Access, Watch, and Reserve (AWaRe) antibiotic classification, 62.91% of AMC was from the access class, with watch class averaging 14.51% in the period 2018-2021. Watch class AMC spiked in 2021 (34.2%) during COVID-19 pandemic compared to 2020 (24.29%). Azithromycin and ciprofloxacin were the most consumed watch class antimicrobials in 2021. CONCLUSIONS: The relatively high consumption of injectable antimicrobials and year over year increase in watch class AMC requires urgent stewardship interventions. Further work is needed to establish a system for longitudinal AMC surveillance that is well resourced and funded to overcome the challenges of estimation and provide more accurate data on consumption and use patterns.

The immediate treatment outcomes and cost estimate for managing clinical measles in children admitted at Mulago Hospital: A retrospective cohort study.

Over the recent years, the Ministry of Health in Uganda has reported multiple measles outbreaks in various districts despite the availability of a safe cost effective vaccine. Measles, especially among the unvaccinated can lead to serious complications including death while its management heavily burdens the family and health care system. This study aims to determine the immediate treatment outcomes and estimate the cost of treating a measles case. A retrospective cohort study using records review was conducted among children 0-12 years admitted at Mulago hospital throughout 2018. Demographics, complications, vaccination status, discharge status, duration of hospital stay, type of treatment, supplies and investigations done were abstracted from the patient charts. Treatment costs were obtained from the hospital pharmacy price list while the unit cost of utilities, human resource, food and security were obtained from the hospital accounts department. Patients' characteristics were summarized descriptively. Cost information, was reported as mean with standard deviation (SD) and range, and was stratified and presented as direct health care (blood test, radiology and treatment) and direct non health care costs. Among 267 reviewed patient charts, the median age was 1.0 ((IQR 0.75-2) years. 63patients (24%) were immunised, 79 (29%) were not immunized, Median length of hospital stay was 4.0 days (IQR 3.0-7.0) with majority (n = 207, 77%) staying < 7 days. 30 patients (11%) died with mortality highest among the unimmunised (n = 13, 44%) and severe pneumonia (39.5%) was the commonest complication. 114.5 USD was estimated to treat a child with measles. Human resource (79.33USD, SD 4.63) and treatment costs (21.98USD, SD 22.77) were the largest expenses. Complications are common in majority of fatal measles cases and these carry a high cost to the healthcare system.

The impact of the increase in import verification fees on local production capacity of selected medicines in Uganda.

BACKGROUND: The local manufacture of pharmaceuticals is an opportunity to develop a broader manufacturing and knowledge-based economy and reduce over dependence on imports. To promote local production, the Ugandan government introduced Buy Uganda Build Uganda policy geared towards promoting use of locally manufactured goods. It also increased import verification fees in 2017 for 37 selected locally manufactured essential medicines from 2 to 12% to discourage importation of these medicines. This study assessed the impact of the increase in verification fees on local production capacity of the medicines. METHODS: This was a mixed methods study looking at production capacity before and after introduction of the 12% import verification fees. It was conducted among six (6) local pharmaceutical industries in Uganda and seven (7) key informant interviews with experts in the pharmaceutical sector between February and September 2021. RESULTS: The overall increase in local production capacity of the selected medicines was 8.2% from 2017 to 2020. The most significant increases were in the production of capsules (100.6%, P = 0.03) and oral liquids (170.8%, P = 0.0001). All the industries registered an increase in number of employees between 2017 and 2020 with an average percentage increase of 42%. There was a 14.7% (95% CI 2.76-17.6%) change in installed capacity of the compression machine (P = 0.033) and 27.7% (95% CI 24.6-33.9%) change in installed capacity of the Blow-Fill-Seal (BFS) filling machines (P = 0.011). There was also an increase in the number and capacity of installed utilities such as the heating ventilation and air conditioning (968%) and standby generators (131%). Only two (2) industries registered an increase in critical quality control equipment and one had all the critical equipment available by 2020. Most of the key informants reported positive impact of the increment of import verification on local manufacturing capacity. CONCLUSIONS: Local pharmaceutical production capacity increased with the increase in import verification fees with significant increases in production of oral liquids and capsules. Successful implementation of policies supporting local production will promote the development of local pharmaceutical industries. Governments should consider increasing the list of medicines to benefit from the import verification fees increase by adding all essential generic medicines for which there is adequate domestic production capacity and technical skills.

A serological survey of brucellosis in wildlife in four major National Parks of Uganda.

BACKGROUND: Brucellosis is a contagious zoonotic disease of great public health and economic significance especially in developing countries. The disease affects humans and several species of livestock and wildlife. Studies on Brucellosis in wildlife in Uganda have been limited to single populations particularly in Queen Elizabeth National Park. This study aimed at estimating the percentage of positive samples of Brucella spp. in wildlife in four major national parks of Uganda. This was a retrospective survey which utilized archived samples collected from wildlife during the annual disease surveillance activities between 2013 and 2017. RESULTS: A total of 241 samples from seven species namely African buffalo (Syncerus caffer, n = 109), African elephant (Loxodonta africana, n = 22), giraffe (Giraffa camelopardalis rothschildi, n = 41), Uganda kob (Kobus kob thomasi, n = 36), lion (Panthera leo, n = 6), plain zebra (Equus quagga, n = 25), and bushbuck (Tragelaphus scriptus, n = 2), were tested for antibodies using the Rose Bengal Plate Test. The overall percentage of positive samples in the four national parks was 31.1% (75/241; 95% CI: 25.6-37.2). Kidepo Valley National Park had a significantly higher percentage of positive samples of 55.9% (19/34; 95% CI: 39.5-71.1) compared to other sampled national parks (p < 0.05). Lions had significantly higher percentage of positive samples at 66.7% (4/6) than African buffalo at 48.6% (53/109, p < 0.0001). There were no antibodies for Brucella spp. detected in African elephant and bushbuck. CONCLUSION: This study shows variations in percentage of positive samples with Brucella spp. between species and across national parks and notably a high percentage with Brucella spp. in wildlife in Uganda than that recorded elsewhere in sub-Saharan region of Africa. Potential for transmission to other wildlife and spill over to livestock is high especially in national parks with high livestock-wildlife interaction.

Preparedness of health care systems for Ebola outbreak response in Kasese and Rubirizi districts, Western Uganda.

BACKGROUND: The level of preparedness of the health care workers, the health facility and the entire health system determines the magnitude of the impact of an Ebola Virus Disease (EVD) outbreak as demonstrated by the West African Ebola outbreak. The objective of the study was to assess preparedness of the health care facilities and identify appropriate preparedness measures for Ebola outbreak response in Kasese and Rubirizi districts in western Uganda. METHODS: A cross sectional descriptive study was conducted by interviewing 189 health care workers using a structured questionnaire and visits to 22 health facilities to determine the level of health care system preparedness to EVD outbreak. District level infrastructure capabilities, existence of health facility logistics and supplies, and health care workers' knowledge of EVD was assessed. EVD Preparedness was assessed on infrastructure and logistical capabilities and the level of knowledge of an individual health work about the etiology, control and prevention of EVD. RESULTS: Twelve out of the 22 of the health facilities, especially health center III's and IV's, did not have a line budget to respond to EVD when there was a threat of EVD in a nearby country. The majority (n = 13) of the facilities did not have the following: case definition books, rapid response teams and/or committees, burial teams, and simulation drills. There were no personal protective equipment that could be used within 8 h in case of an EVD outbreak in fourteen of the 22 health facilities. All facilities did not have Viral Hemorrhagic Fever (VHF) incident management centers, isolation units, guidelines for burial, and one-meter distance between a health care worker and a patient during triage. Overall, 54% (n = 102) of health care workers (HCWs) did not know the incubation period of EVD. HCWs who had tertiary education (aOR = 5.79; CI = 1.79-18.70; p = 0.003), and were Christian (aOR = 10.47; CI = 1.94-56.4; p = 0.006) were more likely to know about the biology, incubation period, causes and prevention of EVD. CONCLUSIONS: Feedback on the level of preparedness for the rural districts helps inform strategies for building capacity of these health centers in terms of infrastructure, logistics and improving knowledge of health care workers.

Pharmacovigilance of suspected or confirmed therapeutic ineffectiveness of artemisinin-based combination therapy: extent, associated factors, challenges and solutions to reporting.

BACKGROUND: Therapeutic ineffectiveness of artemisinin-based combination therapy (ACT) increases the risk of malaria-related morbidity and mortality, and raises healthcare costs. Yet, little has been done to promote the pharmacovigilance (PV) of ACT ineffectiveness in sub-Saharan Africa, particularly in Uganda. This study aimed to determine the extent and associated factors of the past 6 months reporting of suspected or confirmed ACT therapeutic ineffectiveness by healthcare professionals (HCPs), and difficulties and potential solutions to the PV of ACT therapeutic ineffectiveness. METHODS: Survey of 685 HCPs conducted using a self-administered questionnaire from June to July 2018 in a nationally representative sample of public and private health facilities in Uganda. HCPs disclosed if they had spontaneously reported ACT therapeutic ineffectiveness to appropriate authorities in the previous 6 months. Multivariable logistic regression models were used to identify determinants of past 6-months, HCP-reported ACT therapeutic ineffectiveness. RESULTS: One in five (20%, 137/685; 95% CI 17-23%) HCPs reported ACT therapeutic ineffectiveness to an appropriate authority in the previous 6 months. HCPs commonly reported ACT therapeutic ineffectiveness to immediate supervisors (72%, 106/147), mostly verbally only (80%, 109/137); none had ever submitted a written report of ACT therapeutic ineffectiveness to Uganda's National Pharmacovigilance Centre. Common difficulties of reporting ACT therapeutic ineffectiveness were: unavailability of reporting procedures (31%, 129/421), poor follow-up of treated patients (22%, 93/421) and absence of reporting tools (16%, 68/421). Factors associated with reporting ACT therapeutic ineffectiveness in the past 6 months were: hospital-status (vs other; OR = 2.4, 95% CI 1.41-4.21), HCPs aged under 25 years (OR = 2.2, 95% CI 1.29-3.76), suspicion of ACT therapeutic ineffectiveness in the past 4 weeks (OR = 2.3, 95% CI 1.29-3.92), receipt of patient-complaint(s) of ACT therapeutic ineffectiveness in the past 4 weeks (OR = 2.9, 95% CI 1.62-5.12) and HCPs from northern (vs central; OR = 0.5, 95% CI 0.28-0.93) and western (vs central; OR = 0.4, 95% CI 0.17-0.77) parts of Uganda. CONCLUSION: One in five HCPs reported ACT therapeutic ineffectiveness, mostly verbally to supervisors. The existing adverse drug reaction (ADR)-reporting infrastructure could be leveraged to promote the PV of ACT therapeutic ineffectiveness.

Prescription of Levofloxacin and Moxifloxacin in Select Hospitals in Uganda: A Pilot Study to Assess Guideline Concordance.

Background: In Uganda, national tuberculosis (TB) treatment guidelines were revised to include the newer generation fluoroquinolones among the second-line treatment options for multidrug-resistant TB. This study was designed to analyze if the prescription of these quinolones is compliant with country recommendations. Methods: This was an observational retrospective study of consumption data for 2017 and 2018 across four selected regional referral hospitals. The sources of consumption data were hospital pharmacy stock cards and the dispensing register. The medical files of patients who had been prescribed fluoroquinolones were also assessed to study compliance with the Uganda Clinical Guidelines and the British National Formulary (BNF). Results: None of the 371 levofloxacin prescriptions analyzed complied with the Uganda Clinical Guidelines, although 250 (67.3%) were prescribed for indications included in the BNF. According to WHO prescription indicators, only 220 (59.3%) prescriptions were appropriate. Conclusion: The prescription of levofloxacin and moxifloxacin increased in the hospitals studied, but in a high proportion of cases, they were not compliant with country recommendations. The findings call for the strengthening of national antimicrobial stewardship programs.

Healthcare professionals' perspective can guide post-marketing surveillance of artemisinin-based combination therapy in Uganda.

BACKGROUND: Efficient testing to identify poor quality artemisinin-based combination therapy (ACT) is important to optimize efforts to control and eliminate malaria. Healthcare professionals interact with both ACT and malaria patients they treat and hence could observe, first-hand, suspect poor quality artemisinin-based combinations linked to poor malaria treatment outcomes and the factors associated with inappropriate use or treatment failure. METHODS: A cross-sectional study of 685 HCP perspectives about the efficacy of ACT between June and July 2018 at selected health facilities in Uganda. Medicine samples were obtained from the seven regions of Uganda and tested for quality using the Germany Pharma Health Fund™ minilabs. RESULTS: The average age of the 685 respondents was 30 (SD = 7.4) years. There was an almost equal distribution between male and female respondents (51:49), respectively. Seventy percent (n = 480) were diploma holders and the nurses contributed to half (49%, n = 334) of the study population. Sixty-one percent of the HCPs reported having ever encountered ACT failures while treating uncomplicated malaria. Nineteen percent of HCPs thought that dihydroartemisinin/piperaquine gave the most satisfactory patient treatment outcomes, while 80% HCPs thought that artemether/lumefantrine gave the least satisfactory patient treatment outcomes, possibly due to dosing schedule and pill burden. Healthcare professionals from the Central region (OR = 3.0, CI 0.3-1.0; P = 0.0001), Eastern region (OR = 5.4, CI 2.9-9.8; P = 0.0001) and Northern region (OR = 5.3, CI 2.9-9.9; P = 0.0001) had a higher chance of encountering ACT failure in 4 weeks prior to the survey as compared to those from the western region. Healthcare professionals from private health facilities also had higher chances of encountering ACT failures in past 4 weeks as compared to those from public health facilities (OR = 2.7, CI 1.7-3.9; P = 0.0001). All 192 samples passed the quality screening tests. The random sample of 10% of all samples randomly obtained by the laboratory staff also passed the chemical content analysis and dissolution tests. CONCLUSION: ACT medicines are widely available over-the-counter to the public and it is very difficult to report and monitor a decrease in efficacy or treatment failure. The perspectives of HCPs on treatment failure or lack of efficacy may potentially guide optimization efforts of sampling methodologies for the quality survey of ACT medicines.

The effect of community dialogues and sensitization on patient reporting of adverse events in rural Uganda: Uncontrolled before-after study.

BACKGROUND: Patients experiencing adverse drug events (ADE) in many developing countries are in the best position to report these events to the authorities but need to be empowered to do so. Systematic evaluation of community engagement and patient support especially in rural areas would provide evidence for a program to monitor potential harm from medicines. The aim of this study was to assess the effects of a community dialogue and sensitization (CDS) program on the knowledge, attitude and practises of community members for reporting ADE. METHODS: This an uncontrolled before-after study was conducted in two eastern Ugandan districts between September 2016 and August 2017. RESULTS: After implementation of the community dialogue and sensitization (CDS) program, there was an overall 20% (95% CI:16% to 25%) increase in knowledge about ADE in the community compared to before the program began. Awareness levels increased by 50% (95% CI: 37% to 63%) among those with little or no education and by41% (95% CI: 31% to 52%) among young people (15-24 years). Furthermore, 5% (95% CI: 3% to 7%) more respondents recognized the need for reporting ADEs compared to before the program. Finally, there was a significant increase of 115% (95% CI:137% to 217%) in respondent recognition and reporting of ADEs compared to the beginning of the CDS program. Overall, this community found the CDS program acceptable and proposed aspects that could be improved for future use. CONCLUSION: Our evaluation showed that the CDS program increased knowledge and improved attitudes by catalyzing discussions among community members and healthcare professionals on health issues and monitoring safety of medicines compared to before the program. Successful implementation of the program depends on holistic health systems strengthening and adaptation to the community's way of life.

Lowland grazing and Marburg virus disease (MVD) outbreak in Kween district, Eastern Uganda.

BACKGROUND: Uganda is one of the few countries in Africa that has been experiencing outbreaks of viral hemorrhagic fevers such as Ebola, Marburg and Crimean-Congo Hemorrhagic fevers. In 2017 Uganda experienced a Marburg Virus Disease (MVD) outbreak with case fatality rate of 100% in Kween district. Although hunting for wild meat was linked to the MVD outbreak in Kween district, less was reported on the land use changes, especially the changing animal grazing practices in Kween district. METHODS: Through Makerere University One Health graduate fellowship program with attachment to Uganda Red Cross Society, a study was conducted among the agricultural communities to elucidate the risk behaviors in Kween district that can be linked to the 2017 Marburg disease outbreak. RESULTS: Results show that although a few elderly participants ascribed fatal causes (disobedience to gods, ancestors, and evil spirits) to the MVD outbreak during FGDs, majority of participants linked MVD to settling in caves (inhabited by Fruit Bats) during wet season as upper belts are extensively used for crop production leaving little space for animal grazing. Members also noted side activities like hunting for wild meat during this grazing period that could have predisposed them to Marburg Virus. CONCLUSIONS: There is need to integrate One Health concepts within agricultural extension service provision in Uganda so as to enhance the management of such infectious diseases.

The Burden of Adverse Drug Reactions Due to Artemisinin-Based Antimalarial Treatment in Selected Ugandan Health Facilities: An Active Follow-Up Study.

INTRODUCTION: Uganda has rapidly increased access to antimalarial medicines in an effort to address the huge malaria disease burden. Pharmacovigilance information is important to guide policy decisions. OBJECTIVES: The purpose of this study was to establish the burden of adverse drug reactions (ADRs) and associated risk factors for developing ADRs to artemisinin-based antimalarial treatment in Uganda. METHODS: An active follow-up study was conducted between April and July 2017 in a cohort of patients receiving treatment for uncomplicated malaria in the Iganga, Mayuge, and Kampala districts. RESULTS: A total of 782 patients with a median age of 22 years (58.6% females) were recruited into this study, with the majority recruited from public health facilities (97%). Diagnostic tests before treatment were performed for 76% of patients, and 97% of patients received artemether/lumefantrine. The prevalence of ADRs was 22.5% (176/782); however, the total number of ADRs was 245 since some patients reported more than one ADR. The most commonly reported reactions were general body weakness (24%), headache (13%), and dizziness (11%). Women were more likely to develop an ADR (adjusted odds ratio [aOR] 1.8, 95% confidence interval [CI] 1.1-2.9), urban dwellers were more likely to develop an ADR than rural residents (aOR 9.9, 95% CI 5.4-17.9), and patients with comorbidities were more likely to develop an ADR than those without (aOR 7.4, 95% CI 4.4-12.3). CONCLUSION: The burden of ADRs is high among women and in patients from urban settings and those with comorbidities. Such risk factors need to be considered in order to optimise therapy. Close monitoring of ADRs is key in implementation of the malaria treatment policy.