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.

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.

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.

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.

Antibiotic use among children under five years with diarrhea in rural communities of Gulu, northern Uganda: a cross-sectional study.

BACKGROUND: Diarrhea is the second leading cause of mortality in children under 5 years of age globally, and the risk of death increases with practices such as restriction of fluid intake and inappropriate use of antibiotics. We determined the prevalence of antibiotic use in managing diarrhea in children under 5 years of age in rural communities of Gulu district, northern Uganda. METHOD: A cross-sectional study among children under 5 years with diarrhea, from households selected using multi-stage sampling. A researcher administered questionnaire was used to obtain data from caregivers of these children. RESULTS: Of the 856 children recruited, 318 (37.1%, 318/856) had experienced diarrhea, where 263 (82.7%, 263/318) had diarrhea with acute respiratory infections (ARIs), and 55 (17.3%, 55/318) had diarrhea without ARIs. The majority (89.6%, 285/318) of the children had non-bloody diarrhea. A high proportion (82.8%) of the children with non-bloody diarrhea also had ARIs. Bloody diarrhea was reported for 33 (10.4%) children including those with ARIs, and only 6 of these (18.2%) children had bloody diarrhea without ARIs. Of the 318 children with diarrhea, over half (52%, CI: 46-57) were administered antibiotics. Of the 55 children who had diarrhea without ARIs, over a third (38%, CI: 26-51) were administered antibiotics. Similarly, of the 263 children with diarrhea and ARIs, 54% (CI: 48-60) were treated with antibiotics. The determinants of antibiotic use included; children living in peri-urban settings (AOR: 3.41, CI: 1.65-7.08, P = 0.001), getting treatment from health facility (AOR: 1.76, CI: 1.06-2.93, P = 0.029), and having diarrhea with ARIs (AOR: 3.09, CI: 1.49-6.42, P = 0.003). CONCLUSION: Antibiotic use is common among children under 5 years with diarrhea in rural communities of northern Uganda.

Registration of antimicrobials, Kenya, Uganda and United Republic of Tanzania, 2018.

OBJECTIVE: To determine the proportion of essential and non-essential antimicrobial medicines that are registered on the drug registers in Kenya, Uganda and United Republic of Tanzania. METHODS: We categorized all antimicrobials on the national drug registers and essential medicines lists of the three countries using the British National Formulary. We also categorized all antibiotics according to the World Health Organization access, watch and reserve (AWaRe) classification. We calculated the proportions of essential and non-essential antimicrobials that were registered by antimicrobial class and AWaRe classification. FINDINGS: In 2018, Kenya had 2105 registered antimicrobials, Uganda had 1563 and the United Republic of Tanzania had 1327. Of these medicines, 1353 (64.3%) were non-essential in Kenya, 798 (51.1%) in Uganda and 706 (53.2%) in the United Republic of Tanzania. Kenya had 160 antimicrobials on its national essential medicines lists, Uganda had 187 and the United Republic of Tanzania had 182; of these, 33 (20.7%), 50 (26.7%) and 52 (28.6%) were not registered, respectively. High proportions of antimycobacterial and antiparasitic medicines were not registered. Of essential access antibiotics, 14.3% (4/28) were not registered in Kenya, 8.6% (3/35) in Uganda and 20.5% (8/39) in the United Republic of Tanzania, nor were 25.0% (3/12) of watch antibiotics in Kenya, 14.3% (2/14) in Uganda and 19.1% (4/21) in the United Republic of Tanzania. CONCLUSION: Suboptimal registration of essential antimicrobials and over-registration of non-essential antimicrobials may encourage inappropriate use, especially since non-essential antimicrobials do not appear on national treatment guidelines. Countries should prioritize registration of the antimicrobial medicines on their essential medicines lists.

K13-propeller gene polymorphisms in Plasmodium falciparum parasite population in malaria affected countries: a systematic review of prevalence and risk factors.

BACKGROUND: Efficacy of artemisinin (ART) agents, a critical element of current malaria control efforts is threatened by emergence and spread of resistance. Mutations in pfkelch13 gene associated with ART-resistance evolved in Southeast Asia (SEA). k13 mutations whose role in ART-resistance remains unknown, have subsequently emerged independently across all malaria-affected regions. The aim of this systematic review was to determine the prevalence and identify risk factors of Plasmodium falciparum k13 mutations in malaria-endemic countries. METHODS: An electronic search of studies from 2014 to date was done in MEDLINE via PubMED, SCOPUS, EMBASE and LILACS/VHL databases. Mesh terms and Boolean operators (AND, OR) were used. Two librarians independently conducted this search (RS and AK). The articles were screened for inclusion using a priori criteria set following PRISMA-P and STREGA guidelines. Three independent reviewers (NL, BB, and OM) extracted the data. Data analysis was performed in Open Meta Analyst software. Random effects analysis (DL) was used and heterogeneity established using I2-statistic. RESULTS: A total of 482 articles were retrieved from Pubmed = 302, Lilacs/Vhl = 50, Embase = 80, and Scopus = 37; Bibliography/other searches = 13, of which 374 did not meet the inclusion criteria. The aggregate prevalence of single nucleotide polymorphisms (SNPs) in pfkelch13 gene was 27.6% (3694/14,827) (95% CI 22.9%, 32.3%). Sub-group analysis showed that aggregate prevalence of non-synonymous SNPs in pfkelch13 gene was higher, 45.4% (95% CI 35.4%, 55.3%) in Southeast Asia as opposed to 7.6% (95% CI 5.6%, 9.5%) in the African region. A total of 165 independent k13 mutations were identified across malaria-affected regions globally. A total of 16 non-validated k13 mutations were associated with increased ART parasite clearance half-life (t1/2 > 5 h). The majority, 45.5% (75/165), of the mutations were reported in single P. falciparum parasite infections. Of the 165 k13-mutations, over half were reported as new alleles. Twenty (20) non-propeller mutations in the pfkelch13 gene were identified. CONCLUSION: This review identified emergence of potential ART-resistance mediating k13 mutations in the African region. Diversity of mutations in pfkelch13 gene is highest in African region compared to SEA. Mutations outside the pfkelch13 propeller region associated with increased ART parasite clearance half-life occur in malaria-affected regions.

Persistence of chloroquine resistance alleles in malaria endemic countries: a systematic review of burden and risk factors.

BACKGROUND: Chloroquine, a previous highly efficacious, easy to use and affordable anti-malarial agent was withdrawn from malaria endemic regions due to high levels of resistance. This review collated evidence from published-reviewed articles to establish prevalence of Pfcrt 76T and Pfmdr-1 86Y alleles in malaria affected countries following official discontinuation of chloroquine use. METHODS: A review protocol was developed, registered in PROSPERO (#CRD42018083957) and published in a peer-reviewed journal. Article search was done in PubMed, Scopus, Lilacs/Vhl and Embase databases by two experienced librarians (AK, RS) for the period 1990-to-Febuary 2018. Mesh terms and Boolean operators (AND, OR) were used. Data extraction form was designed in Excel spread sheet 2007. Data extraction was done by three reviewers (NL, BB and MO), discrepancies were resolved by discussion. Random effects analysis was done in Open Meta Analyst software. Heterogeneity was established using I2-statistic. RESULTS: A total of 4721 citations were retrieved from article search (Pubmed = 361, Lilac/vhl = 28, Science Direct = 944, Scopus = 3388). Additional targeted search resulted in three (03) eligible articles. After removal of duplicates (n = 523) and screening, 38 articles were included in the final review. Average genotyping success rate was 63.6% (18,343/28,820) for Pfcrt K76T and 93.5% (16,232/17,365) for Pfmdr-1 86Y mutations. Prevalence of Pfcrt 76T was as follows; East Africa 48.9% (2528/5242), Southern Africa 18.6% (373/2163), West Africa 58.3% (3321/6608), Asia 80.2% (1951/2436). Prevalence of Pfmdr-1 86Y was; East Africa 32.4% (1447/5722), Southern Africa 36.1% (544/1640), West Africa 52.2% (1986/4200), Asia 46.4% (1276/2217). Over half, 52.6% (20/38) of included studies reported continued unofficial chloroquine use following policy change. Studies done in Madagascar and Kenya reported re-emergence of chloroquine sensitive parasites (IC50 < 30.9 nM). The average time (years) since discontinuation of chloroquine use to data collection was 8.7 ± 7.4. There was high heterogeneity (I2 > 95%). CONCLUSION: The prevalence of chloroquine resistance alleles among Plasmodium falciparum parasites have steadily declined since discontinuation of chloroquine use. However, Pfcrt K76T and Pfmdr-1 N86Y mutations still persist at moderate frequencies in most malaria affected countries.

Sero-prevalence of brucellosis among slaughterhouse workers in Bahr el Ghazal region, South Sudan.

BACKGROUND: Brucellosis is an infectious zoonotic disease and is common especially among pastoral communities in most low and middle-income countries. The aim of this study was to determine sero-prevalence, and risk factors of Brucella infection among Slaughterhouse workers, in Bahr el Ghazal region, South Sudan. METHODS: A cross sectional study was conducted among Slaughterhouse workers in Bahr el Ghazal region, South Sudan from December 2015 to May 2016. A pre-tested questionnaire was used in data collection. Each randomly selected participant was interviewed and a venous blood sample collected. The blood samples were screened for Brucellosis infection using Rose Bengal Plate Test (RBPT) and confirmed using Competitive Enzyme link Immuno Sorbet Assay (c-ELISA). Data was analyzed using Stata version 13 at 95% level of confidence. RESULTS: A total of 234 Slaughterhouse workers were screen for Brucella infection. Overall, a third, 32.1% (75/234) of the participants were sero-positive for brucellosis. The prevalence of brucellosis was higher, 17.1% (40/234) in Wau state compared to other states. There was high prevalence among males, 28.6% (67/234) compared to females 3.4% (8/234). The mean age of study participants was 34.4 ± 9.6 years. A high proportion, 12.8% (30/234) of participants with confirmed brucellosis infection were 31-40 years of age. Brucellosis prevalence was high among butchers, 14.5% (34/234), and meat handlers, 9.0% (21/234). CONCLUSIONS: Brucellosis is common among animal slaughterhouse workers in Bahr el Ghazal region, South Sudan. There is need for public awareness campaigns and educational programs to help sensitize communities on Brucella infection.

Medicine use practices in management of symptoms of acute upper respiratory tract infections in children (≤12 years) in Kampala city, Uganda.

BACKGROUND: Medicines are commonly accessed and used for management of illness in children without a prescription. This potentially increases the risk of unwanted treatment outcomes. We investigated medicine use practices in management of symptoms of acute upper respiratory tract infections among children (≤12 years) in households in Nakawa division, Kampala city. METHODS: This was a cross-sectional study conducted among 390 randomly selected children. Data on use of medicines in children (≤12 years) during recent episode of acute upper respiratory tract infection was collected from their care takers using an interviewer administered questionnaire. A recall period of two weeks (14 days) was used in during data collection. RESULTS: The prevalence of giving children non-prescription antimicrobial medicines was 44.8% (38.3-52.2). The most common disease symptoms that the children reportedly had included flu, 84.9% (331/390), cough, 83.1% (324/390), and undefined fever, 69.7% (272/390). Medicines commonly given to children included, paracetamol 53.1% (207/390), Coartem 29.7% (116/390), cough linctus 20.8% (81/390), amoxicillin 18.9% (74/390), Co-trimoxazole 18.5% (72/390), and diphenhydramine 15.4% (60/390). The major sources of medicines given to the children was hospital/clinic, 57.26% (223/390). Most of the children, 81% were given more than one medicine at a time. The majority, 62.3% (243/390) of the care takers who gave the children medicine during the recent illness were not aware of any medicine (s) that should not be given to children. The predictors of non-prescription use of antimicrobial medicines in managing symptoms of acute upper respiratory tract infections in children included, medicines obtained from drug shop (PR: 1.45, CI: 1.14-1.85), medicines at home (PR: 1.8, CI: 0.83-1.198) and type of medicine (antimalarial) (PR: 2.8, CI: 1.17-6.68). CONCLUSION: Children are commonly given multiple medicines during episodes of acute upper respiratory tract infections with most antimicrobial agents accessed and used without a prescription in Kampala city, Uganda.

Prevalence of K13-propeller gene polymorphisms among Plasmodium falciparum parasites isolated from adult symptomatic patients in northern Uganda.

BACKGROUND: In the absence of an effective vaccine, malaria treatment and eradication is still a challenge in most endemic areas globally. This is especially the case with the current reported emergence of resistance to artemisinin agents in Southeast Asia. This study therefore explored the prevalence of K13-propeller gene polymorphisms among Plasmodium falciparum parasites in northern Uganda. METHODS: Adult patients (≥18 years) presenting to out-patients department of Lira and Gulu regional referral hospitals in northern Uganda were randomly recruited. Laboratory investigation for presence of plasmodium infection among patients was done using Plasmodium falciparum exclusive rapid diagnostic test, histidine rich protein-2 (HRP2) (Pf). Finger prick capillary blood from patients with a positive malaria test was spotted on a filter paper Whatman no. 903. The parasite DNA was extracted using chelex resin method and sequenced for mutations in K13-propeller gene using Sanger sequencing. PCR DNA sequence products were analyzed using in DNAsp 5.10.01software, data was further processed in Excel spreadsheet 2007. RESULTS: A total of 60 parasite DNA samples were sequenced. Polymorphisms in the K13-propeller gene were detected in four (4) of the 60 parasite DNA samples sequenced. A non-synonymous polymorphism at codon 533 previously detected in Cambodia was found in the parasite DNA samples analyzed. Polymorphisms at codon 522 (non-synonymous) and codon 509 (synonymous) were also found in the samples analyzed. The study found evidence of positive selection in the Plasmodium falciparum population in northern Uganda (Tajima's D = -1.83205; Fu and Li's D = -1.82458). CONCLUSIONS: Polymorphism in the K13-propeller gene previously reported in Cambodia has been found in the Ugandan Plasmodium falciparum parasites. There is need for continuous surveillance for artemisinin resistance gene markers in the country.

Household antimicrobial self-medication: a systematic review and meta-analysis of the burden, risk factors and outcomes in developing countries.

BACKGROUND: Antimicrobial self-medication is common in most low and middle income countries (LMICs). However there has been no systematic review on non-prescription antimicrobial use in these settings. This review thus intended to establish the burden, risk factors and effects of antimicrobial self-medication in Low and Middle Income Countries. METHODS: In 2012, we registered a systematic review protocol in PROSPERO (CRD42012002508). We searched PubMed, Medline, Scopus, and Embase databases using the following terms; "self-medication", "non-prescription", 'self-treatment', "antimicrobial", "antimalarial", "antibiotic", "antibacterial" "2002-2012" and combining them using Boolean operators. We performed independent and duplicate screening and abstraction of study administrative data, prevalence, determinants, type of antimicrobial agent, source, disease conditions, inappropriate use, drug adverse events and clinical outcomes of antibiotic self-medication where possible. We performed a Random Effects Meta-analysis. RESULTS: A total of thirty four (34) studies involving 31,340 participants were included in the review. The overall prevalence of antimicrobial self-medication was 38.8 % (95 % CI: 29.5-48.1). Most studies assessed non-prescription use of antibacterial (17/34: 50 %) and antimalarial (5/34: 14.7 %) agents. The common disease symptoms managed were, respiratory (50 %), fever (47 %) and gastrointestinal (45 %). The major sources of antimicrobials included, pharmacies (65.5 %), leftover drugs (50 %) and drug shops (37.5 %). Twelve (12) studies reported inappropriate drug use; not completing dose (6/12) and sharing of medicines (4/12). The main determinants of antimicrobial self-medication include, level of education, age, gender, past successful use, severity of illness and income. Reported negative outcomes of antimicrobial self-medication included, allergies (2/34: 5.9 %), lack of cure (4/34: 11.8 %) and causing death (2/34: 5.9 %). The commonly reported positive outcome was recovery from illness (4/34: 11.8 %). CONCLUSION: The prevalence of antimicrobial self-medication is high and varies in different communities as well as by social determinants of health and is frequently associated with inappropriate drug use.

Factors predicting home storage of medicines in Northern Uganda.

BACKGROUND: Medicines are kept in households Worldwide for first aid, treatment of chronic or acute disease conditions. This promotes inappropriate use of medicines and hence the associated risks. The study explored the factors which predict availability and utilization of medicines in households of Northern Uganda. METHOD: A cross sectional survey of 892 households was performed from November-to-December 2012. Five data collectors administered the questionnaires, respondents were requested to bring out any medicines present in their households. Demographic characteristics, drug name, quantity, source, formulation, legibility of drug labels and reasons why the medicines were being kept at home was collected. Data was analyzed using STATA 12.0 at 95% level of significance. RESULTS: Of the households visited, 35.1% (313/892) had drugs. Paracetamol (11.8%), coartem (11.3%), cotrimoxazole (10%), amoxicillin (9.2%) and metronidazole (8.2%) were the major medicines found. Antibacterial drugs were the most commonly (40.1%) kept type of drugs. The medicines present in households were for on-going treatment (48%); 'leftover' (30.5%) and anticipated future use (21.6%). Symptoms of malaria (34.1%) were common in households which had drugs. The medicines kept in homes were mainly from the private sector 60.5% (497/821). The rate of home drug storage was higher 85.3% (267/313) amongst the educated individuals. There was high prevalence 76% (238/313) of self-medication among respondents in households which stored drugs. The average number of medicines in each household was 6 ± 5 with majority (68.1%) having between 1-10 drugs. Previous successful treatment (OR: 1.3; 95% CI: 0.95-1.77), regular income (OR: 1.8; 95% CI: 1.2-2.6) and sex (OR: 0.63; 95% CI: 0.5-0.9) predicted storage of medicines in households in northern Uganda. CONCLUSION: Over a third of households in Northern Uganda store medicines with antibacterial agents being the most common. Self-medication is common among individuals in households which keep drugs. Past successful treatment, regular income and sex predict community home drug storage.

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.

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.

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.

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 the presence of the K13 mutation associated with artemisinin resistance by P. falciparum in Adjumani district, Uganda, necessitates regular surveillance of the effectiveness and efficacy of artemether-lumefantrine in the country.

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.

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.

The diagnostic accuracy of serum and plasma microRNAs in detection of cervical intraepithelial neoplasia and cervical cancer: A systematic review and meta-analysis.

Studies suggest a need for new diagnostic approaches for cervical cancer including microRNA technology. In this review, we assessed the diagnostic accuracy of microRNAs in detecting cervical cancer and Cervical Intraepithelial Neoplasia (CIN). We performed a systematic review following the Preferred Reporting Items for Systematic Review and Meta-Analysis guideline for protocols (PRISMA-P). We searched for all articles in online databases and grey literature from 01st January 2012 to 16th August 2022. We used the quality assessment of diagnostic accuracy studies tool (QUADAS-2) to assess the risk of bias of included studies and then conducted a Random Effects Meta-analysis. We identified 297 articles and eventually extracted data from 24 studies. Serum/plasma concentration miR-205, miR-21, miR-192, and miR-9 showed highest diagnostic accuracy (AUC of 0.750, 0.689, 0.980, and 0.900, respectively) for detecting CIN from healthy controls. MicroRNA panels (miR-21, miR-125b and miR-370) and (miR-9, miR-10a, miR-20a and miR-196a and miR-16-2) had AUC values of 0.897 and 0.886 respectively for detecting CIN from healthy controls. For detection of cervical cancer from healthy controls, the most promising microRNAs were miR-21, miR-205, miR-192 and miR-9 (AUC values of 0.723, 0.960, 1.00, and 0.99 respectively). We report higher diagnostic accuracy of upregulated microRNAs, especially miR-205, miR-9, miR-192, and miR-21. This highlights their potential as stand-alone screening or diagnostic tests, either with others, in a new algorithm, or together with other biomarkers for purposes of detecting cervical lesions. Future studies could standardize quantification methods, and also study microRNAs in higher prevalence populations like in sub-Saharan Africa and South Asia. Our review protocol was registered in PROSPERO (CRD42022313275).