Access to quality-assured artemisinin-based combination therapy and associated factors among clients of selected private drug outlets in Uganda.

BACKGROUND: Malaria treatment in sub-Saharan Africa is faced with challenges including unreliable supply of efficacious agents, substandard medicines coupled with high price of artemisinin-based combinations. This affects access to effective treatment increasing risk of malaria parasite resistance development and adverse drug events. This study investigated access to quality-assured artemisinin-based combination therapy (QAACT) medicines among clients of selected private drug-outlets in Uganda. METHODS: This was a cross sectional study where exit interviews were conducted among clients of private drug outlets in low and high malaria transmission settings in Uganda. This study adapted the World Health Organization/Health Action International (WHO/HAI) standardized criteria. Data was collected using a validated questionnaire. Data entry screen with checks was created in Epi-data ver 4.2 software and data entered in duplicate. Data was transferred to STATA ver 14.0 and cleaned prior to analysis. The analysis was done at 95% level of significance. RESULTS: A total of 1114 exit interviews were conducted among systematically sampled drug outlet clients. Over half, 54.9% (611/1114) of the participants were males. Majority, 97.2% (1083/1114) purchased an artemisinin-based combination anti-malarial. Most, 55.5% (618/1114) of the participants had a laboratory diagnosis of malaria. Majority, 77.9% (868/1114) of the participants obtained anti-malarial agents without a prescription. Less than a third, 27.7% (309/1114) of the participants obtained a QAACT. Of the participants who obtained QAACT, more than half 56.9% (173/309) reported finding the medicine expensive. The predictors of accessing a QAACT anti-malarial among drug outlet clients include type of drug outlet visited (aPR = 0.74; 95%CI 0.6, 0.91), not obtaining full dose (3-day treatment) of ACT (aPR = 0.49; 95%CI 0.33, 0.73), not finding the ACT expensive (aPR = 1.24; 95%CI 1.03, 1.49), post-primary education (aPR = 1.29; 95%CI 1.07,1.56), business occupation (aPR = 1.24; 95%CI 1.02,1.50) and not having a prescription (aPR = 0.76; 95%CI 0.63, 0.92). CONCLUSION: Less than a third of the private drug outlet clients obtained a QAACT for management of malaria symptoms. Individuals who did not find artemisinin-based combinations to be expensive were more likely to obtain a QAACT anti-malarial. The Ministry of Health needs to conduct regular surveillance to monitor accessibility of QAACT anti-malarial agents under the current private sector copayment mechanism.

Prevalence and risk factors of gross neurologic deficits in children after severe malaria: a systematic review protocol.

Background: Children exposed to severe malaria may recover with gross neurologic deficits (GND). Several risk factors for GND after cerebral malaria (CM), the deadliest form of severe malaria, have been identified in children. However, there is inconsistency between previously reported and more recent findings. Although CM patients are the most likely group to develop GND, it is not clear if other forms of severe malaria (non-CM) may also contribute to the malaria related GND. The aim of this systematic review is to synthesize evidence on the prevalence and risk factors for GND in children following CM and map the changes in patterns over time. In addition, this review will synthesize evidence on the reported prevalence and risk factors of gross neurologic deficits following other forms of severe malaria. Methods: The systematic review will be conducted according to recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols (PRISMA-P). Relevant research articles will be identified using relevant search terms from the following databases: MEDLINE, Embase, Web of Science and Global Index Medicus (GIM). The articles will be screened at title and abstract, then at full text for inclusion using a priori eligibility criteria. Data extraction will be done using a tool developed and optimized in Excel spreadsheet. Risk of bias assessment will be done using appropriate tools including ROBINS-E ('Risk Of Bias In Non-randomized Studies of Exposure') tool, while publication bias will be assessed using funnel plot. A random-effects meta-analysis and structured narrative synthesis of the outcomes will be performed and results presented. Discussion: Findings from this systematic review will inform policy makers on planning, design and implementation of interventions targeting the treatment and rehabilitation of GND following severe malaria in children. Systematic review registration: The protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42022297109.

Copayment mechanism in selected districts of Uganda: Availability, market share and price of quality assured artemisinin-based combination therapies in private drug outlets.

BACKGROUND: Malaria remains one of the leading causes of morbidity, and mortality in Uganda. A large proportion of malaria symptomatic patients seek healthcare in private sector. However, availability and affordability are major barriers to access to effective treatment. The private sector copayment mechanism in Uganda aims to increase availability and affordability of antimalarial agents. Our study assessed availability, price, and market share of quality assured artemisinin-based combination therapies (QAACTs) in private drug outlets in selected districts during the implementation of copayment mechanism. METHODS: This was a cross-sectional survey of anti-malarial agents in private drug outlets in in selected moderate-to-high (Tororo, and Apac districts) and low (Kabale and Mbarara districts) malaria transmission settings. Following the World Health Organization/Health Action International (WHO/HAI) criteria, an audit of the antimalarial agents was done using a checklist to determine availability, price, and market share of QAACTs. Data were entered in Epi-data and analyzed in STATA ver 14.0 at 95% confidence level. RESULTS: A total of twenty-eight (28) private drug outlets (pharmacies and drug shops) were included in the survey. One in seven (20/144: 95%CI: 9.1, 20.6) of the antimalarial agents in private drug outlets were quality assured artemisinin-based combination therapies (QAACT). Artemether-lumefantrine (AL), 8.9% (11/124) and Artesunate-Amodiaquine (AQ), 7.3% (9/124) were the only QAACTs present in the drug outlets at the time of the survey. The majority, 86.1%% (124/144) of antimalarial agents present in stock in the drug outlets were artemisinin based. The most common, 38.9% (56/144) ACT in the drug outlets was Dihydroartemisinin-Piperaquine (DHP). Most, 69.4% (100/144) of the antimalarial agents were in high malaria transmission settings. The cost of ACT antimalarial agents is high in the country, USD 1.4 (Artemether-Lumefantrine, AL), USD 2.4 (Dihydroartemisinin-Piperaquine, DP), the first line and second-line agents respectively for treatment of uncomplicated malaria in Uganda. There was a statistically significant difference between the dispensing price of 'Green leaf' ACTs (QAACT) and the recommended price (p<0.001). Predictors of availability of QAACT in private drug outlets include pharmacy drug outlet (aPR:0.4; 95%CI: 0.2, 0.9) and dispensing price more than 3000UGX (USD 0.83) (aPR: 0.4, 95%CI: 0.1, 0.51). CONCLUSION: Quality assured artemisinin-based combination therapies (QAACTs) are not common in private drug outlets in selected districts in Uganda. All the drug outlets had at least one ACT antimalarial agent present on the day of the survey. The dispensing price of QAACTs was significantly higher than the recommended markup price. There is need for awareness creation, surveillance, and monitoring of the implementation of Copayment mechanism in the country.

Diagnostic accuracy of chest ultrasound scan in the diagnosis of childhood tuberculosis.

Chest Ultrasound Scan (CUS) has been utilized in place of CXR in the diagnosis of adult pneumonia with similar or higher sensitivity and specificity to CXR. However, there is a paucity of data on the use of CUS for the diagnosis of childhood TB. This study aimed to determine the diagnostic accuracy of CUS for childhood TB. This cross-sectional study was conducted at the Mulago National Referral Hospital in Uganda. Eighty children up to 14 years of age with presumptive TB were enrolled. They all had CUS and CXR performed and interpreted independently by radiologists. The radiologist who performed the CXR was blinded to the CUS findings, and vice versa. Radiologists noted whether TB was likely or unlikely. A two-by-two table was developed to compare the absolute number of children as either TB likely or TB unlikely on CXR or CUS. This was used to calculate the sensitivity and specificity of CUS when screening for TB in children, with a correction to accommodate the use of CXR as a reference test. The sensitivity of CUS was 64% (95% CI 48.5%-77.3%), while its specificity was 42.7% (95% CI 25.5%-60.8%). Both the CUS and CXR found 29 children with a likelihood of TB, and 27 children unlikely to have TB. CUS met the sensitivity target set by the WHO TPP for Triage, and it had a sensitivity and specificity comparable to that of CXR.

Spectrum of and Factors Associated with Eye Disorders among Rheumatoid Arthritis Patients Attending Tertiary Hospital in Uganda.

Background: Ocular morbidities associated with rheumatoid arthritis (RA) have not received much attention in Africa, particularly in sub-Saharan Africa. They are among the commonest (40%) extra-articular organ involvement in RA. If undiagnosed, there is a potential risk of them causing visual impairment or blindness. There is no documented study in Uganda on the magnitude of eye disorders among RA patients. Aim: To determine the spectrum of eye disorders and associated factors among patients with RA attending Mulago National Referral Hospital. Methods: A hospital based cross-sectional study was conducted among adults with RA attending the rheumatology clinic between July 2021 and September 2021. Clinical and sociodemographic data were collected, and ophthalmologic examinations were performed on all consenting participants. Modified Poisson regression with robust standard error was used to determine factors associated with eye disorders. Results: Overall, 105 patients with RA were enrolled, of which, 53 (50.5%) had eye disorders. The commonest disorder (54.7%, n=29) was dry-eye syndrome. Factors that were significantly associated with eye disorders were age 36-55 years (aPR 1.56, p=0.015), duration of RA >5 years (aPR 1.81, p=0.001), use of hydroxychloroquine >5 years (aPR 1.77, p=0.041), dose of oral steroids >10 mg/day (aPR 1.49, p=0.034), and history of both diabetes and hypertension (aPR 1.87, p=0.014). Conclusion: The prevalence of eye disorders among patients with RA was high, with the commonest being dry-eye syndrome. We recommend that ocular examinations be performed on every patient at the time of RA diagnosis for early detection of eye disorders.

Bone mineral density among children living with HIV failing first-line anti-retroviral therapy in Uganda: A sub-study of the CHAPAS-4 trial.

BACKGROUND: Children living with perinatally acquired HIV (CLWH) survive into adulthood on antiretroviral therapy (ART). HIV, ART, and malnutrition can all lead to low bone mineral density (BMD). Few studies have described bone health among CLWH in Sub-Saharan Africa. We determined the prevalence and factors associated with low BMD among CLWH switching to second-line ART in the CHAPAS-4 trial (ISRCTN22964075) in Uganda. METHODS: BMD was determined using dual-energy X-ray Absorptiometry (DXA). BMD Z-scores were adjusted for age, sex, height and race. Demographic characteristics were summarized using median interquartile range (IQR) for continuous variables and proportions for categorical variables. Logistic regression was used to determine the associations between each variable and low BMD. RESULTS: A total of 159 children were enrolled (50% male) with median age (IQR) 10 (7-12) years, median duration of first -line ART 5.2(3.3-6.8) years; CD4 count 774 (528-1083) cells/mm3, weight-for-age Z-score -1.36 (-2.19, -0.65) and body mass index Z-score (BMIZ) -1.31 (-2.06, -0.6). Low (Z-score≤ -2) total body less head (TBLH) BMD was observed in 28 (18%) children, 21(13%) had low lumbar spine (LS) BMD, and15 (9%) had both. Low TBLH BMD was associated with increasing age (adjusted odds ratio [aOR] 1.37; 95% CI: 1.13-1.65, p = 0.001), female sex (aOR: 3.8; 95% CL: 1.31-10.81, p = 0.014), low BMI (aOR 0.36:95% CI: 0.21-0.61, p<0.001), and first-line zidovudine exposure (aOR: 3.68; 95% CI: 1.25-10.8, p = 0.018). CD4 count, viral load and first- line ART duration were not associated with TBLH BMD. Low LS BMD was associated with increasing age (aOR 1.42; 95% CI: 1.16-1.74, p = 0.001) and female sex: (aOR 3.41; 95% CI: 1.18-9.8, p = 0.023). CONCLUSION: Nearly 20% CLWH failing first-line ART had low BMD which was associated with female sex, older age, first-line ZDV exposure, and low BMI. Prevention, monitoring, and implications following transition to adult care should be prioritized to identify poor bone health in HIV+adolescents entering adulthood.

Pharmacopeial quality of artemether-lumefantrine anti-malarial agents in Uganda.

BACKGROUND: Substandard anti-malarial agents pose a significant challenge to effective malaria control and elimination efforts especially in sub-Saharan Africa. The quality of anti-malarials in most low-and-middle income countries (LMICs) is affected by several factors including inadequate regulation and limited resources. In this study, the pharmacopeial quality of artemether-lumefantrine (AL) in low and high malaria transmission settings in Uganda was assessed. METHODS: This was a cross-sectional study conducted among randomly selected private drug outlets. The AL anti-malarials available in drug outlets were purchased using overt method. The samples were screened for quality using visual inspection, weight uniformity, content assay and dissolution tests. The assay test was done using liquid chromatography-mass spectrometry (LC-MS). The samples were considered substandard if the active pharmaceutical ingredient (API) content was outside 90-110% range of the label claim. Dissolution test was conducted following United States Pharmacopoeia (USP) method. Data was analysed using descriptive statistics and presented as means with standard deviations, frequencies, and proportions. Correlation between medicine quality and independent variables was determined using Fisher's exact test of independence at 95% level of significance. RESULTS: A total of 74 AL anti-malarial samples were purchased from high (49/74; 66.2%) and low (25/74; 33.8%) malaria transmission settings. The most common batch of AL was LONART, 32.4% (24/74), with 33.8% (25/74) being 'Green leaf'. Overall prevalence of substandard quality artemether-lumefantrine was 18.9% (14/74; 95% CI: 11.4-29.7). Substandard quality AL was significantly associated with setting (p = 0.002). A total of 10 samples (13.5%) failed artemether content assay test while, 4 samples (5.4%, 4/74) failed the lumefantrine assay test. One sample from a high malaria transmission setting failed both artemether and lumefantrine assay content test. Of the samples that failed artemether assay test, 90% had low (< 90%) artemether content. All the samples passed visual inspection and dissolution tests. CONCLUSION: Artemether-lumefantrine agents, the recommended first-line treatment for uncomplicated malaria with APIs outside the recommended pharmacopeial content assay limit is common especially in high malaria transmission settings. There is need for continuous surveillance and monitoring of the quality of artemisinin-based anti-malarials across the country by the drug regulatory agency.

Ocular complications and associated factors among traditional eye medicines users attending the eye clinic at Mulago national referral hospital, Uganda.

Background: Over the past decades there has been a phenomenal increase in the use of Traditional Eye medicines (TEM) worldwide and there are several factors that compel patients to use TEM. Objectives: We conducted a study to determine the types of traditional eye medicine, ocular complications, and associated factors among traditional eye medicine users at the Mulago National Referral Hospital (MNRH) eye clinic. Methods and Materials: A hospital-based cross-sectional study among TEM users at MNRH eye clinic from June to August 2021. Epi Data version 4.2 and STATA version 15 used for analysis. A modified Poisson regression with robust standard errors was used to determine the associated factors. Results: Overall, 182 TEM users (males:53.3%) were enrolled, with a mean age of 36±21SD years. The most frequently used type of TEM were plant products (47.8%). 70% of TEM users had ocular complications, the most frequent manifestation was conjunctivitis (53.9%). Ocular complications were significantly associated with living in the urban areas (p< 0.006) and participants who reported ease and availability of TEM (p < 0.001). Conclusion: Plant-based products were the most frequently used types of TEM, a large proportion of the TEM users were found with sight-threatening ocular complications.

Adult Computed Tomography examinations in Uganda: Towards determining the National Diagnostic Reference Levels.

INTRODUCTION: Diagnostic Reference Levels (DRLs), typically set at the 75th percentile of the dose distribution from surveys conducted across a broad user base using a specified dose-measurement protocol, are recommended for radiological examinations. There is a need to develop and implement DRLs as a standardisation and optimisation tool for the radiological protection of patients at Computed Tomography (CT) facilities. METHODS: This was a retrospective cross-sectional study conducted in seven (7) different CT scan facilities in which participants were recruited by systematic random sampling. The study variables were dose length product (DLP) and volume-weighted CTDI (CTDIvol) for the radiation doses for head, chest, abdomen and lumbar spine CT examinations. The DRLs for CTDIvol and DLP were obtained by calculating the 3rd quartiles of the radiation doses per study site by anatomical region. The national diagnostic reference levels were determined by computation of DRLs using the 75th centile of the median values. RESULTS: A total of 574 patients were examined with an average age of 47.1 years. For CTDIvol estimates; there was a strong positive significant relationship between the CTDIvol and examination mAs (rs = 0.9017, p-value < 0.001), and reference mAs (rs = 0.0.7708, p-value < 0.001). For DLP estimates; there was a moderate positive significant relationships between DLP and total mAs (rs = 0.6812, p-value < 0.001), reference mAs (rs = 0.5493, p-value < 0.001). The DRLs were as follows; for head CT scan - the average median CTDIvol was 56.02 mGy and the DLP was 1260.3 mGy.cm; for Chest CT, the CTDI volume was 7.82 mGy and the DLP was 377.0 mGy.cm; for the abdomen CT, the CTDI volume 12.54 mGy and DLP 1418.3 mGy.cm and for the lumbar spine 19.48 mGy and the DLP was 843 mGy.cm, respectively. CONCLUSION: This study confirmed the need to optimize the CT scan parameters in order to lower the national DRLs. This can be achieved by extensive training of all the CT scan radiographers on optimizing the CT scan acquisition parameters. Continuous dose audits are also advised with new equipment or after every three years to ensure that values out of range are either justified or further investigated.

Interventions to increase youth employment: An evidence and gap map.

Background: Globally, 13% of the youth are not in education, employment or training (NEET). Moreover, this persistent problem has been exacerbated by the shock of Covid-19 pandemic. More youth from disadvantaged backgrounds are likely unemployed than those from better off backgrounds. Thus, the need for increased use of evidence in the design and implementation of youth employment interventions to increase effectiveness and sustainability of interventions and outcomes. Evidence and gap maps (EGMs) can promote evidence-based decision making by guiding policy makers, development partners and researchers to areas with good bodies of evidence and those with little or no evidence. The scope of the Youth Employment EGM is global. The map covers all youth aged 15-35 years. The three broad intervention categories included in the EGM are: strengthening training and education systems, enhancing labour market and, transforming financial sector markets. There are five outcome categories: education and skills; entrepreneurship; employment; welfare and economic outcomes. The EGM contains impact evaluations of interventions implemented to increase youth employment and systematic reviews of such single studies, published or made available between 2000 and 2019. Objectives: The primary objective was to catalogue impact evaluations and systematic reviews on youth employment interventions to improve discoverability of evidence by decision makers, development patterners and researchers, so as to promote evidence-based decision making in programming and implementation of youth employment initiatives. Search Methods: Twenty databases and websites were searched using a validated search strategy. Additional searches included searching within 21 systematic reviews, snowballing 20 most recent studies and citation tracking of 10 most recent studies included in the EGM. Selection Criteria: The study selection criteria followed the PICOS approach of population, intervention, relevant comparison groups, outcomes and study design. Additional criterion is; study publication or availability period of between 2000 and 2021. Only impact evaluations and systematic reviews that included impact evaluations were selected. Data Collection and Analysis: A total of 14,511 studies were uploaded in EPPI Reviewer 4 software, upon which 399 were selected using the criteria provided above. Coding of data took place in EPPI Reviewer basing on predefined codes. The unit of analysis for the report is individual studies where every entry represents a combination of interventions and outcomes. Main Results: Overall, 399 studies (21 systematic reviews and 378 impact evaluations) are included in the EGM. Impact evaluations (n = 378) are much more than the systematic reviews (n = 21). Most impact evaluations are experimental studies (n = 177), followed by non-experimental matching (n = 167) and other regression designs (n = 35). Experimental studies were mostly conducted in both Lower-income countries and Lower Middle Income countries while non-experimental study designs are the most common in both High Income and Upper Middle Income countries. Most evidence is from low quality impact evaluations (71.2%) while majority of systematic reviews (71.4% of 21) are of medium and high quality rating. The area saturated with most evidence is the intervention category of 'training', while the underrepresented are three main intervention sub-categories: information services; decent work policies and; entrepreneurship promotion and financing. Older youth, youth in fragility, conflict and violence contexts, or humanitarian settings, or ethnic minorities or those with criminal backgrounds are least studied. Conclusions: The Youth Employment EGM identifies trends in evidence notably the following: Most evidence is from high-income countries, an indication of the relationship between a country's income status and research productivity.The most common study designs are experimental.Most of the evidence is of low quality. This finding serves to alert researchers, practitioners and policy makers that more rigorous work is needed to inform youth employment interventions. Blending of interventions is practiced. While this could be an indication that blended intervention could be offering better outcomes, this remains an area with a research gap.

PROTOCOL: Interventions to increase youth employment: An evidence and gap map.

The research question guiding the production of the youth employment evidence and gap map (EGM) is stated as follows: What is the nature and extent of the evidence base of impact evaluations and systematic reviews on youth employment programmes in the world? The primary objective of is to catalogue impact evaluations and systematic reviews on youth employment interventions to enhance discoverability of evidence by decision makers, development patterners and researchers, so as to promote evidence-based decision making in programming and delivery of youth employment initiatives. This evidence gap map is also a primary input into the implementation of Mastercard Foundation's strategy titled "Africa Works: Mastercard Foundation Strategy 2018-2030", which points out sharing of evidence-based knowledge and innovation with stakeholders as a key strategy to be used (Mastercard Foundation). The time frame for the development of the youth EGM will run from the last quarter of 2019 to December 2020. The five secondary objectives are: (i) To construct a framework for the classification of youth employment effectiveness studies. The objective will be achieved through the development of an intervention and outcome framework using an engaged consultative process involving the review team, Mastercard Foundation and other stakeholders. (ii) To identify available evidence, and clusters of evidence, including its quality rating. This will involve activities such as identification of studies using a standardised study search strategy, screening and coding of studies in EPPI Reviewer 4, which is a web-based software program for production of reviews. (iii) To create a map of youth employment effectiveness studies equipped with an appealing user-friendly web-based search content visualisation using interactive mapping software. To achieve this object, data coded in EPPI Reviewer 4 will be exported to another software (EPPI mapper) which is designed for generating EGMs. (iv) To produce a narrative report of the youth employment EGM. This will be achieved through analysis of data in EPPI Reviewer 4 and report writing. To disseminate the EGM to users to increase awareness to support evidence-informed decision-making across countries. We will achieve this objective by organising dissemination workshops, participating in conferences and hosting the evidence and gap on our websites.