Day 3 parasitemia and Plasmodium falciparum Kelch 13 mutations among uncomplicated malaria patients treated with artemether-lumefantrine in Adjumani district, Uganda.

Artemisinin resistance threatens malaria control and elimination efforts globally. Recent studies have reported the emergence of Plasmodium falciparum parasites tolerant to artemisinin agents in sub-Saharan Africa, including Uganda. The current study assessed the day 3 parasite clearance and its correlation with P. falciparum K13 propeller gene (pfkelch13) mutations in P. falciparum parasites isolated from patients with uncomplicated malaria under artemether-lumefantrine (AL) treatment. This study enrolled 100 P. falciparum-positive patients to whom AL was prescribed between 09/September/2022 and 06/November/2022. Blood samples were collected in EDTA tubes before treatment initiation (day 0) and on day 3. Parasitemia was assessed by microscopy from blood smears and quantitative polymerase chain reaction (qPCR) from the DNA extracted. The day 0 parasite K13 gene was sequenced using Sanger sequencing. Sequence data were analysed using MEGA version 11 software. The data were analysed using STATA version 15, and the Mann‒Whitney U test was used to compare PCR parasite clearance on day 3 using the comparative CT value method and pfkelch13 mutations. The prevalence of day 3 parasitaemia was 24% (24/100) by microscopy and 63% (63/100) by qPCR from the AL-treated patients. P. falciparum K13-propeller gene polymorphism was detected in 18.8% (15/80) of the day 0 DNA samples. The K13 mutations found were C469Y, 12.5% (10/80); A675V, 2.5% (2/80); A569S, 1.25%, (1/80), A578S, 1.25%, (1/80) and; F491S, 1.25%, (1/80) a new allele not reported anywhere. The C469Y mutation, compared to the wild-type, was associated with delayed parasite clearance p=0.0278, Hodges-Lehmann estimation 3.2108 on the log scale, (95%CI 1.7076, 4.4730). There was a high prevalence of day 3 P. falciparum among malaria patients treated using artemether-lumefantrine. We conclude that the K13 mutation associated with artemisinin resistance by P. falciparum is present in Adjumani district, Uganda. This necessitates regular surveillance of the effectiveness and efficacy of artemether-lumefantrine in the country.

Experience of healthcare personnel on Co-payment mechanism and the implications on its use in private drug outlets in Uganda.

BACKGROUND: Malaria treatment is faced with the challenge of access, affordability, availability, and quality of antimalarial medicines. Affordable medicines facility-malaria (AMFm) program and subsequently Co-payment mechanism were developed to help increase access to quality assured Artemisinin-based combination therapies (ACTs) in seven countries in sub-Saharan Africa. We explored through a qualitative study, experience of healthcare personnel on Co-payment mechanism and the implication on its use in private drug outlets in Uganda. METHOD: Private drug outlets that reported stocking antimalarial agents in moderate-to-high and low malaria transmission settings were purposively selected for inclusion in the study. In each drug outlet, data was collected from a pharmacist/dispenser through key informant interview. The interview was done using a key informant interview guide which covered the following areas, (i) sociodemographic characteristics, ii) awareness of healthcare personnel on the co-payment mechanism, (iii) awareness of healthcare personnel on quality assured artemisinin combination therapies (QAACT), (iv) antimalarial stocking in private drug outlets, (v) antimalarial dispensing prices, (vi) considerations made while stocking, and pricing antimalarial agents, vii) challenges in antimalarial dispensing, and (viii) access to antimalarial agents in private drug outlets. Data was managed using Atlas.ti and analyzed using framework methodology. RESULTS: Data was collected from 25 key informants (12 pharmacists and 13 dispensers). Five themes emerged following data analysis, (i) antimalarial stocking influenced by price and client demand, (ii) access and purchasing behavior of drug outlet clients, (iii) basis of dispensing antimalarial agents in private drug outlets, (iv) awareness of QAACT, and (v) awareness of Co-payment mechanism. None of the study participants was aware of the existence of Co-payment mechanism and QAACT in the private sector. Duocotecin brand of ACTs was the most mentioned and dispensed ACT among the study participants in private drug outlets. Nearly all the pharmacists/dispensers said that many clients who request to purchase ACTs don't come with a prescription and prefer buying cheaper antimalarial agents. Study participants reported stocking and selling both ACTs and non-ACT antimalarial agents in the drug outlets. Pharmacists/dispensers in the drug outlets reported that most clients could not afford buying a full dose of an ACT. None of the study participants considered using Co-payment mechanism while stocking ACTs in the drug outlets. CONCLUSION: There is lack of awareness and utilization of Co-payment mechanism in stocking, pricing, and dispensing of ACTs among pharmacists/dispensers in private drug outlets in Uganda. The antimalarial dispensing in drug outlets was mostly based on prescriptions, clients' preferences, and medicine affordability. The Ministry of Health needs to create demand for Co-payment mechanism through public awareness campaigns, training of healthcare personnel and behavior change communication in the private sector.

Audit of essential medicine listing and registration status of medicines on standard treatment guidelines in Kenya, Tanzania and Uganda: Case study of malaria, tuberculosis, hypertension and type 2 diabetes mellitus.

Objectives: To determine alignment between national and World Health Organization (WHO) treatment recommendations, medicines prioritisation in country's essential medicines list (EML), and medicines availability in National drug register. Design: An audit of medicines for malaria, tuberculosis, hypertension and type 2 diabetes mellitus listed in the national standard treatment guidelines (STGs) of Kenya, Tanzania and Uganda, as of March 2021, against WHO treatment guidelines, and respective country EML and National drug register. Setting: Not applicable. Participants: None. Main outcome measures: Proportion of medicine in country's STGs that align with WHO treatment recommendations, country's EML and country's drug register. Results: Some disease areas had two sets of treatment guidelines - national STGs and disease-specific treatment guidelines (DSGs) developed at different times with different recommended medicines. Both STGs and DSGs included medicines not recommended by the WHO or not listed on the country EML and drug register. Non-WHO-recommended medicines accounted for 17/68 (25%), 10/57 (18%) and 3/30 (10%) of all STG medicines in Kenya, Tanzania and Uganda, respectively. For tuberculosis, the numbers and proportion of STG medicines listed on the respective national EMLs were 2/6 (33%), 15/19 (79%) and 4/5 (80%) in Kenya, Tanzania and Uganda. All tuberculosis medicines included in Kenya's and Uganda's STGs were registered compared with only 12/19 (63%) tuberculosis medicines in Tanzania's STG. Conclusions: Alignment between treatment guidelines, EMLs and drug registers is crucial for effective national pharmaceutical policy. Research is needed to understand the inclusion of medicines on STGs and DSGs which fall outside WHO treatment guidelines; the non-alignment of some STGs and DSGs, and STGs and DSGs including medicines which are not on country EML and drug register.

Plasmodium falciparum genetic diversity and multiplicity of infection based on msp-1, msp-2, glurp and microsatellite genetic markers in sub-Saharan Africa: a systematic review and meta-analysis.

BACKGROUND: In sub-Saharan Africa (SSA), Plasmodium falciparum causes most of the malaria cases. Despite its crucial roles in disease severity and drug resistance, comprehensive data on Plasmodium falciparum genetic diversity and multiplicity of infection (MOI) are sparse in SSA. This study summarizes available information on genetic diversity and MOI, focusing on key markers (msp-1, msp-2, glurp, and microsatellites). The systematic review aimed to evaluate their influence on malaria transmission dynamics and offer insights for enhancing malaria control measures in SSA. METHODS: The review was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Two reviewers conducted article screening, assessed the risk of bias (RoB), and performed data abstraction. Meta-analysis was performed using the random-effects model in STATA version 17. RESULTS: The review included 52 articles: 39 cross-sectional studies and 13 Randomized Controlled Trial (RCT)/cohort studies, involving 11,640 genotyped parasite isolates from 23 SSA countries. The overall pooled mean expected heterozygosity was 0.65 (95% CI: 0.51-0.78). Regionally, values varied: East (0.58), Central (0.84), Southern (0.74), and West Africa (0.69). Overall pooled allele frequencies of msp-1 alleles K1, MAD20, and RO33 were 61%, 44%, and 40%, respectively, while msp-2 I/C 3D7 and FC27 alleles were 61% and 55%. Central Africa reported higher frequencies (K1: 74%, MAD20: 51%, RO33: 48%) than East Africa (K1: 46%, MAD20: 42%, RO33: 31%). For msp-2, East Africa had 60% and 55% for I/C 3D7 and FC27 alleles, while West Africa had 62% and 50%, respectively. The pooled allele frequency for glurp was 66%. The overall pooled mean MOI was 2.09 (95% CI: 1.88-2.30), with regional variations: East (2.05), Central (2.37), Southern (2.16), and West Africa (1.96). The overall prevalence of polyclonal Plasmodium falciparum infections was 63% (95% CI: 56-70), with regional prevalences as follows: East (62%), West (61%), Central (65%), and South Africa (71%). CONCLUSION: The study shows substantial regional variation in Plasmodium falciparum parasite genetic diversity and MOI in SSA. These findings suggest a need for malaria control strategies and surveillance efforts considering regional-specific factors underlying Plasmodium falciparum infection.

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.

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.

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.

The role of medicines and therapeutics committees structure in supporting optimal antibacterial use in hospitals in Uganda: A mixed method study.

Although the roles of Medicines and therapeutic committees (MTCs) have been expanding, there is limited information on the role of their structure in optimal antibacterial use in hospitals, especially in low-and-middle-income countries. Our study explored the structure and role of MTC in supporting antibacterial use in regional referral, general hospitals and tertiary private not-for-profit (PNFP) hospitals in Uganda. We conducted an explanatory sequential mixed-method approach with triangulation to explore the structure and functional role of MTCs from August 2019 to February 2020 in hospitals in Uganda. Quantitative data was collected using an interviewer-administered questionnaire among chairpersons or secretaries of MTCs and was analysed using descriptive statistics. We conducted key informant interviews using an interview guide among long-term serving members of MTCs to collect qualitative data which triangulated the quantitative data. The study revealed that sixteen hospitals had successfully established MTCs with an average duration of the MTCs' existence of 5.6 (+2.7) years. The membership of the MTCs varied between 7 and 14, with a median value of 10, and the majority of members in MTCs were pharmacists (15 out of 16) and clinical specialists (13 out of 16). The most frequent subcommittees of the 16 hospitals MTC were supply chain (n = 14), antimicrobial stewardship (n = 13), and infection control (n = 12). Majority (14 out of 16) of the MTCs supported availability and access of antibacterial use by selecting and evaluating antibacterials agents for their formulary lists using established criteria. Additionally, 15 out 16 MTCs conducted antimicrobial stewardship activities to support optimal antimicrobial use. In our study, MTC membership and subcommittees were critical structural components that aided the selection and evaluation antibacterials on hospital formulary lists and they supported optimal antibacterial use through implementing various antimicrobial stewardship activities. There is a need for the Ministry of Health to conduct more training on operationalising MTCs structures in all hospitals.

Medicinal plants used in the management of cancers by residents in the Elgon Sub-Region, Uganda.

BACKGROUND: In Uganda, medicinal plants have been utilized to treat a variety of ailments, including cancer. However, there is little information available about the medicinal plants used to treat cancer in the Elgon subregion. As a result, the current study documented the plant species used in the management of cancer in the Elgon sub-region. METHODS: Data were gathered by observation, self-administered questionnaires, interview guides, and guided field trips. Analyzing descriptive statistics and creating graphs were done using SPSS (version 21.0) and GraphPad Prism® version 9.0.0, respectively. Well-established formulae were used to calculate quantitative indices. The narratives were interpreted using major theories and hypotheses in ethnobotany. RESULTS: A total of 50 plant species from 36 families were documented, and herbal knowledge was mainly acquired through inheritance. Fabaceae and Asteraceae comprised more plant species used in herbal preparation. Most plants were collected from forest reserves (63%); herbal therapies were made from herbs (45%); and leaves were primarily decocted (43%). The most frequently used plants were Tylosema fassoglensis, Hydnora abyssinica, Azidarachata indica, Prunus Africana, Kigelia africana, Syzygium cumini, Hydnora africana, Rhoicissus tridentata, Albizia coriaria, and Plectranthus cuanneus. All the most commonly used plants exhibited a high preference ranking (60-86%) and reliability level (74.1-93.9%). Generally, the ICF for all the cancers treated by medicinal plants was close to 1 (0.84-0.95). CONCLUSIONS: The ten most commonly utilized plants were favored, dependable, and most important for treating all known cancers. As a result, more investigation is required to determine their phytochemistry, toxicity, and effectiveness in both in vivo and in vitro studies. This could be a cornerstone for the pharmaceutical sector to develop new anticancer medications.

Data sharing practices in collaborative human genomic research in low- and middle-income countries: A systematic review protocol.

INTRODUCTION: The practice of creating large databases has become increasingly common by combining research participants' data into larger repositories. Funders now require that data sharing be considered in newly funded research project, unless there are justifiable reasons not to do so. Access to genomic data brings along a host of ethical concerns as well as fairness and equity in the conduct of collaborative research between researchers from high- income and low-and middle-income countries. MATERIALS AND METHODS: This systematic review protocol will be developed in line with PRISMA -guidelines which refers to Open Science Framework, registered in PROSPERO (https://www.crd.york.ac.uk/prospero/) record CRD42022297984 and published in a peer reviewed journal. Data sources will include PubMed, google scholar, EMBASE, Web of science and MEDLINE. Both published and grey literature will be searched. Subject matter experts including bioethicists, principal investigators of genomic research projects and research administrators will be contacted. After de-duplication, titles and abstracts will be screened for eligibility. Data extraction will be undertaken using a piloted form designed in EPPI-Reviewer software before conducting risk of bias assessments by a pair of reviewers, acting independently. Any discrepancies will be resolved by consensus. Analysis will be done using a structured narrative synthesis and where feasible metanalysis. This review will attempt to highlight the context of data sharing practices in the global North-South and South-South collaborative human genomic research in low- and middle-income countries. This review will enhance the body of evidence on ethical, legal and social implications of data sharing in international collaborative genomic research setting criteria for data sharing. The full report will be shared with relevant stakeholders including universities, civil society, funders, and departments of genomic research to ensure an adequate reach in low-and middle-income countries (LMICs).

Experiences of healthcare personnel on the efficacy of artemisinin-based combination therapy and malaria diagnosis in hospitals in Uganda.

BACKGROUND: The risk of widespread resistance to artemisinin-based combination therapy (ACT) remains high in Uganda following detection of Plasmodium falciparum parasites with delayed artemisinin clearance genotype and phenotype. Establishment of context specific interventions to mitigate emergence and spread of artemisinin resistance is thus key in the fight against malaria in the country. The aim of this study was to explore the experiences of healthcare personnel on malaria diagnosis and self-reported efficacy of ACT in the management of malaria symptomatic patients in hospitals in low and high malaria transmission settings in Uganda. METHODS: This was a qualitative study in which data was collected from healthcare personnel in hospitals using key informant interviews. The key informant interview guide was developed, pre-tested prior to use and covered the following areas, (i) sociodemographic characteristics, (ii) malaria diagnosis (clinical and parasite based), (iii) quality-assured artemisinin-based combination therapy, (iv) malaria patient follow-up, (v) artemisinin resistance, (vi) anti-malarial self-medication. Data was entered in Atlas.ti ver 9.0 and analysis done following a framework criterion. RESULTS: A total of 22 respondents were interviewed of which 16 (72.7%) were clinicians. Majority, 81.8% (18/22) of the respondents were male. The following themes were developed from the analysis, malaria diagnosis (procedures and challenges), use of malaria laboratory test results, malaria treatment in hospitals, use of quality assured ACT (QAACT) in malaria treatment, and efficacy of ACT in malaria treatment. CONCLUSION: Most healthcare personnel-initiated malaria treatment after a positive laboratory test. Cases of malaria patients who report remaining symptomatic after prior use of ACT exist especially in high malaria transmission settings in Uganda. There is need for regular monitoring of artemisinin resistance emergence and spread in the country.

Efficacy of nano encapsulated herbal extracts in the treatment of induced wounds in animal models: a systematic review protocol.

BACKGROUND: Wounds inflict pain and affect human health causing high expenditure on treatment and management. Herbal crude extracts are used in traditional medicine as a treatment for wounds and other illnesses. However, the progress in the use of plants has been deterred due to their poor solubility and poor bioavailability requiring administration at high doses. It has been established that nanoencapsulation of herbal products in nanocarriers (size 1 nm to 100 nm) such as nanofibers, nanoparticles, nanospheres, and nanoliposomes greatly improves their efficacy. Due to their small and large surface area, nanocarriers are more biologically active, improve bioavailability, protect the drug from deterioration, and release it to the targeted site in a sustainable manner. AIM: The review aims to collate and appraise evidence on the efficacy of nano encapsulated herbal extracts in the treatment of induced wounds in animal models. METHODS: The review will be protocol-driven and conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis for Protocols (PRISMA-P) and protocol guidelines for systematic review and meta-analysis for animal intervention studies. The final review will be conducted and reported with reference to PRISMA 2020 statement. Studies will be searched in Pub Med, ProQuest, Web of Science, Medline Ovid, EMBASE, and Google Scholar. The PRISMA flow criteria will be followed in screening the articles for inclusion. Data extraction form will be designed in Excel spreadsheet 2013 and data extracted based on the primary and secondary outcomes. Risk of bias assessment will be done using SYRCLE's risk of bias tool for animal studies. Data analysis will be done using narrative and quantitative synthesis. EXPECTED RESULTS: We hope to make meaningful comparisons between the effectiveness of the herb-loaded nanomaterials and other interventions (controls) in the selected studies, based on the primary and secondary outcome measures. We expect that these findings to inform clinical practice on whether preclinical studies show enough quality evidence on the efficacy and safety of herbal-loaded nanomaterials that can be translated into clinical trials and further research. SYSTEMIC REVIEW REGISTRATION: PROSPERO 330330. The protocol was submitted on the 11th of May 2022.

A Cross-Sectional Study on Knowledge and Attitudes About Organ Donation and Transplantation in an Urban Population in a Low-Income Country.

BACKGROUND: Uganda's Health Sector Development Plan (2015/16 through 2019/2020) noted that most referrals for treatment abroad were for organ transplant services that cost the government >5.6 million USD. The government of Uganda has invested in building the capacity for organ donation and transplantation services by training human resources personnel and setting up infrastructure in Kampala, where these services can be accessed. However, there is no information on the readiness of communities and the scientific community to embrace (communities) or undertake (science) organ transplantation in the country. We set out to assess knowledge and attitudes about organ donation and transplantation among the urban population in Kampala. METHODS: We conducted a cross-sectional survey among 395 participants from the urban population of Kampala at Garden City Mall, Wandegeya market, and Nakawa market from 28 May through 7 June 2021. We asked about knowledge of organ donation and transplantation, collected sociodemographic data, and performed a sentiment analysis of participants' attitudes toward organ donation and transplantation. RESULTS: The M:F ratio of participants was 1:1; the majority (55.9%) of participants were Baganda, two-thirds of participants knew about organ donation, and 90% of participants did not know of any government policy on organ donation and transplantation. Radio/television was the most common source of information, and the kidney was the most frequently transplanted organ. Overall, there were 94.3% and 93.2% positive sentiments toward organ transplantation and organ donation, respectively. The need for stricter laws governing organ donation and transplantation, corruption, and fear were the main negative sentiments expressed by participants. CONCLUSIONS: Sensitization of the community is required regarding government policy on organ donation and transplantation, and this should be communicated through radio/television and social media. There was a positive attitude toward organ donation and transplantation.

Efficacy of antimalarial herbal medicines used by communities in malaria affected regions globally: a protocol for systematic review and evidence and gap map.

INTRODUCTION: With the rising resistance to artemisinin-based combination treatments, there is a need to hasten the discovery and development of newer antimalarial agents. Herbal medicines are key for the development of novel drugs. Currently, herbal medicine usage in communities for treatment of malaria symptoms is common as an alternative to conventional (modern) antimalarial agents. However, the efficacy and safety of most of the herbal medicines has not yet been established. Therefore, this systematic review and evidence gap map (EGM) is intended to collate and map the available evidence, identify the gaps and synthesise the efficacy of herbal antimalarial medicines used in malaria affected regions globally. METHODS AND ANALYSIS: The systematic review and EGM will be done following PRISMA and Campbell Collaboration guidelines respectively. This protocol has been registered in PROSPERO. Data sources will include PubMed, MEDLINE Ovid, EMBASE, Web of Science, Google Scholar and grey literature search. Data extraction will be done in duplicate using a data extraction tool tailored in Microsoft Office excel for herbal antimalarials discovery research questions following the PICOST framework. The Risk of Bias and overall quality of evidence will be assessed using Cochrane risk of bias tool (clinical trials), QUIN tool (in vitro studies), Newcastle-Ottawa tool (observational studies) and SYRCLE's risk of bias tool for animal studies (in vivo studies). Data analysis will be done using both structured narrative and quantitative synthesis. The primary review outcomes will be clinically important efficacy and adverse drug reactions. Laboratory parameters will include Inhibitory Concentration killing 50% of parasites, IC50; Ring Stage Assay, RSA0-3 hou; Trophozoite Survival Assay, TSA50. ETHICS AND DISSEMINATION: The review protocol was approved by the School of Biomedical Science Research Ethics Committee, Makerere University College of Health Sciences (SBS-2022-213). PROSPERO REGISTRATION NUMBER: CRD42022367073.

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.

The diagnostic accuracy of serum microRNAs in detection of cervical cancer: a systematic review protocol.

BACKGROUND: Cervical cancer remains a public health problem worldwide, especially in sub-Saharan Africa. There are challenges in timely screening and diagnosis for early detection and intervention. Therefore, studies on cervical cancer and cervical intraepithelial neoplasia suggest the need for new diagnostic approaches including microRNA technology. Plasma/serum levels of microRNAs are elevated or reduced compared to the normal state and their diagnostic accuracy for detection of cervical neoplasms has not been rigorously assessed more so in low-resource settings such as Uganda. The aim of this systematic review was therefore to assess the diagnostic accuracy of serum microRNAs in detecting cervical cancer. METHODS: We will perform a systematic review following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. We will search for all articles in MEDLINE/PubMed, Web of Science, Embase, and CINAHL, as well as grey literature from 2012 to 2022. Our outcomes will be sensitivity, specificity, negative predictive values, positive predictive values or area under the curve (Nagamitsu et al, Mol Clin Oncol 5:189-94, 2016) for each microRNA or microRNA panel. We will use the quality assessment of diagnostic accuracy studies (Whiting et al, Ann Intern Med 155:529-36, 2011) tool to assess the risk of bias of included studies. Our results will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Diagnostic Test Accuracy studies (PRISMA-DTA). We will summarise studies in a flow chart and then describe them using a structured narrative synthesis. If possible, we shall use the Lehmann model bivariate approach for the meta analysis USE OF THE REVIEW RESULTS: This systematic review will provide information on the relevance of microRNAs in cervical cancer. This information will help policy makers, planners and researchers in determining which particular microRNAs could be employed to screen or diagnose cancer of the cervix. SYSTEMATIC REVIEW REGISTRATION: This protocol has been registered in PROSPERO under registration number CRD42022313275.

Effects of anti-malarial prophylaxes on maternal transfer of Immunoglobulin-G (IgG) and association to immunity against Plasmodium falciparum infections among children in a Ugandan birth cohort.

BACKGROUND: The in-utero transfer of malaria specific IgG to the fetus in Plasmodium falciparum infected pregnant women potentially plays a role in provision of immune protection against malaria in the first birth year. However, the effect of Intermittent Prophylactic Treatment in Pregnancy (IPTp) and placental malaria on the extent of in-utero antibody transfer in malaria endemic regions like Uganda remain unknown. The aim of this study was thus to establish the effect of IPTp on in-utero transfer of malaria specific IgG to the fetus and the associated immune protection against malaria in the first birth year of children born to mothers who had P. falciparum infection during pregnancy in Uganda. METHODS: We screened a total of 637 cord blood samples from a double blinded randomized clinical trial on Sulfadoxine-Pyrimethamine (SP) and Dihydroartemisinin-Piperaquine (DP) IPTp in a Ugandan birth cohort; study conducted from Busia, Eastern Uganda. Luminex assay was used to measure the cord levels of IgG sub-types (IgG1, IgG2, IgG3 and IgG4) against 15 different P. falciparum specific antigens, with tetanus toxoid (t.t) as a control antigen. Man-Whitney U test (non-parametric) in STATA (ver15) was used in statistical analysis of the samples. In addition, Multivariate cox regression analysis was used to determine the effect of maternal transfer of IgG on the incidence of malaria in the first birth year of children under study. RESULTS: Mothers on SP expressed higher levels of cord IgG4 against erythrocyte binding antigens (EBA140, EBA175 and EBA181) (p<0.05). Placental malaria did not affect cord levels of IgG sub-types against selected P. falciparum specific antigens (p>0.05). Children who expressed higher levels (75th percentile) of total IgG against the six key P. falciparum antigens (Pf SEA, Rh4.2, AMA1, GLURP, Etramp5Ag1 and EBA 175) had higher risk of malaria in the first birth year; AHRs: 1.092, 95% CI: 1.02-1.17 (Rh4.2); 1.32, 95% CI: 1.00-1.74 (PfSEA); 1.21, 95%CI: 0.97-1.52 (Etramp5Ag1); 1.25, 95%CI: 0.98-1.60 (AMA1); 1.83, 95%CI: 1.15-2.93 (GLURP) (GLURP), and 1.35,; 95%CI: 1.03-1.78 (EBA175). Children born to mothers categorized as poorest had the highest risk of malaria infections in the first birth year (AHR: 1.79, 95% CI: 1.31-2.4). Children born to mothers who had malaria infections during gestation had higher risk of getting malaria in the first birth year (AHR 1.30; 95%CI: 0.97-1.7). CONCLUSION: Malaria prophylaxis in pregnant mothers using either DP or SP does not affect expression of antibodies against P. falciparum specific antigens in the cord blood. Poverty and malaria infections during pregnancy are key risk factors of malaria infections in the first birth year of growth of children. Antibodies against P. falciparum specific antigens does not protect against parasitemia and malaria infections in the first birth year of children born in malaria endemic areas.

Prevalence of, and factors associated with, alcohol use disorder among young adults (aged 15-24 years) living with HIV/AIDS in low-income and middle-income countries: protocol for a systematic review.

INTRODUCTION: Alcohol use is a global driver of HIV infection and disease progression, mediated through risky behaviour and poor antiretroviral adherence. Most studies about the burden of alcohol use among people living with HIV (PLWH)/AIDS have been done in adult populations, but less is known about young people with HIV, especially in low-income and middle-income countries (LMICs), despite the high level of alcohol use in these settings. The aim of this review is to collate evidence on the prevalence of, and factors associated with, alcohol use disorder (AUD) among young adults (aged 15-24 years) living with HIV/AIDS in LMICs. METHODS AND ANALYSIS: Two experienced librarians will conduct an independent article search in PubMed, PsycINFO, Embase and Web of Science databases, using relevant Medical Subject Headings terms and Boolean operators ('AND', 'OR'). We will include English-language articles that were published in peer-reviewed journals from 1 January 2000, to 25 July 2022, that documented the prevalence of AUD among young people (15-24 years) living with HIV in LMICs. We shall exclude systematic review articles and qualitative studies. Two independent reviewers will screen the articles for eligibility and data will be extracted onto a preset Excel spreadsheet. Data analysis will be done using Stata V.14.0. Heterogeneity will be assessed by use of the I2 statistic and data will be pooled in meta-analyses where appropriate. Publication bias will be assessed using the funnel plot. ETHICS AND DISSEMINATION: Ethical approval is not needed as this systematic review will be based on published studies. Findings from this study will be disseminated via submission for publication in a peer-reviewed journal, at conference presentations, and made available to health professionals, scientists and policy makers. Our data set can be made available on request. REGISTRATION DETAILS: PROSPERO, CRD42022308955.

Mortality among non-severely under nourished children with pneumonia globally: protocol for a systematic review and meta-analysis.

Background: Pneumonia remains the commonest cause of ill health and mortality among children worldwide. Severe undernutrition increases the mortality risk among children with pneumonia. While children with pneumonia are at increased risk of developing malnutrition, the impact of pneumonia on mortality and nutritional status of non-severely undernourished children is not well described. The impact of nutritional supplementation on mortality and nutritional status in this population is not well understood. This review will collate available evidence on the all-cause mortality and anthropometric indices outcomes following pneumonia, as well as the impact of nutritional supplementation on mortality and anthropometry among non-severely malnourished children with pneumonia. Methods: The review will be done using a priori criteria developed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Data will be obtained from data bases, grey literature, and bibliographies. An experienced librarian will conduct article search in PUBMED, MEDLINE, EMBASE, Web of Science, Google scholar, and Scopus. Retrieved articles will be entered in Endnote ver 9.0, duplicates removed, and transferred to Epi-reviewer for screening and data abstraction. Risk of bias in the included articles will be assessed using standard criteria. Heterogeneity will be assessed using I 2-statistic and sub-group analysis will be done. Data will be analysed using both narrative and quantitative synthesis. Quantitative synthesis will be done using DeSimonian and Laird Random-effects model in STATA ver 15.0. Conclusions: The results will provide baseline information about the mortality and anthropometric outcomes of pneumonia among non-severely malnourished children as well as the potential effect of nutritional supplementation on these outcomes. This will provide a basis to explore the potential for nutritional supplementation improving clinical outcomes like mortality and occurrence of severe acute malnutrition among children with severe pneumonia worldwide. Registration: The review has been registered in PROSPERO (CRD42021257272; 15 July 2021).

Adipose-derived stromal vascular fraction (SVF) in scar treatment: a systematic review protocol.

BACKGROUND: Autologous adipose-derived stromal vascular fraction (SVF) is an emerging therapy that is being pioneered as a potential treatment for keloids and hypertrophic scars. Up to this point, there isn't a cure for keloids and hypertrophic scars yet they comprise the commonest benign skin disorders. Despite published studies reporting potential therapeutic benefits of SVF, their use and efficacy on scar improvement are not clearly described. The aim of this review is to describe the clinical practice involved in harvesting, processing, utilization of SVF, and associated efficacy in scar treatment. METHODS: We shall include published clinical articles evaluating the efficacy of SVF on improving scar characteristics and assessment scores among adults with keloids or hypertrophic scars. Article search of Medline/PubMed, Cochrane Library and Embase using Mesh terms of "scars" and "stromal vascular fraction" combined with the Boolean operators ("AND", "OR") will be performed by two independent researchers following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. The primary outcome measure will be the mean difference in the Scar characteristics including Scar assessment scores, scar thickness among others. DATA SYNTHESIS: Descriptive data synthesis and mean differences between treatment arms will be calculated for the primary outcome of the scar assessment scores. In case more than three studies provide consistent characteristics of the scar assessment scores, a meta-analysis will be conducted. DISCUSSION: Evidence obtained from the systematic review will form the foundation upon which further clinical trials research will be conducted in evaluating the efficacy of autologous adipose-derived stromal vascular fraction in keloid and hypertrophic scar. The systematic review has been submitted to the PROSPERO database and is currently under review.