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.

Prediction of pre-eclampsia at St. Mary's hospital lacor, a low-resource setting in northern Uganda, a prospective cohort study.

BACKGROUND: Pre-eclampsia is the second leading cause of maternal death in Uganda. However, mothers report to the hospitals late due to health care challenges. Therefore, we developed and validated the prediction models for prenatal screening for pre-eclampsia. METHODS: This was a prospective cohort study at St. Mary's hospital lacor in Gulu city. We included 1,004 pregnant mothers screened at 16-24 weeks (using maternal history, physical examination, uterine artery Doppler indices, and blood tests), followed up, and delivered. We built models in RStudio. Because the incidence of pre-eclampsia was low (4.3%), we generated synthetic balanced data using the ROSE (Random Over and under Sampling Examples) package in RStudio by over-sampling pre-eclampsia and under-sampling non-preeclampsia. As a result, we got 383 (48.8%) and 399 (51.2%) for pre-eclampsia and non-preeclampsia, respectively. Finally, we evaluated the actual model performance against the ROSE-derived synthetic dataset using K-fold cross-validation in RStudio. RESULTS: Maternal history of pre-eclampsia (adjusted odds ratio (aOR) = 32.75, 95% confidence intervals (CI) 6.59-182.05, p = 0.000), serum alkaline phosphatase(ALP) < 98 IU/L (aOR = 7.14, 95% CI 1.76-24.45, p = 0.003), diastolic hypertension ≥ 90 mmHg (aOR = 4.90, 95% CI 1.15-18.01, p = 0.022), bilateral end diastolic notch (aOR = 4.54, 95% CI 1.65-12.20, p = 0.003) and body mass index of ≥ 26.56 kg/m2 (aOR = 3.86, 95% CI 1.25-14.15, p = 0.027) were independent risk factors for pre-eclampsia. Maternal age ≥ 35 years (aOR = 3.88, 95% CI 0.94-15.44, p = 0.056), nulliparity (aOR = 4.25, 95% CI 1.08-20.18, p = 0.051) and white blood cell count ≥ 11,000 (aOR = 8.43, 95% CI 0.92-70.62, p = 0.050) may be risk factors for pre-eclampsia, and lymphocyte count of 800 - 4000 cells/microliter (aOR = 0.29, 95% CI 0.08-1.22, p = 0.074) may be protective against pre-eclampsia. A combination of all the above variables predicted pre-eclampsia with 77.0% accuracy, 80.4% sensitivity, 73.6% specificity, and 84.9% area under the curve (AUC). CONCLUSION: The predictors of pre-eclampsia were maternal age ≥ 35 years, nulliparity, maternal history of pre-eclampsia, body mass index, diastolic pressure, white blood cell count, lymphocyte count, serum ALP and end-diastolic notch of the uterine arteries. This prediction model can predict pre-eclampsia in prenatal clinics with 77% accuracy.

Prediction of stillbirth low resource setting in Northern Uganda.

BACKGROUND: Women of Afro-Caribbean and Asian origin are more at risk of stillbirths. However, there are limited tools built for risk-prediction models for stillbirth within sub-Saharan Africa. Therefore, we examined the predictors for stillbirth in low resource setting in Northern Uganda. METHODS: Prospective cohort study at St. Mary's hospital Lacor in Northern Uganda. Using Yamane's 1967 formula for calculating sample size for cohort studies using finite population size, the required sample size was 379 mothers. We doubled the number (to > 758) to cater for loss to follow up, miscarriages, and clients opting out of the study during the follow-up period. Recruited 1,285 pregnant mothers at 16-24 weeks, excluded those with lethal congenital anomalies diagnosed on ultrasound. Their history, physical findings, blood tests and uterine artery Doppler indices were taken, and the mothers were encouraged to continue with routine prenatal care until the time for delivery. While in the delivery ward, they were followed up in labour until delivery by the research team. The primary outcome was stillbirth 24 + weeks with no signs of life. Built models in RStudio. Since the data was imbalanced with low stillbirth rate, used ROSE package to over-sample stillbirths and under-sample live-births to balance the data. We cross-validated the models with the ROSE-derived data using K (10)-fold cross-validation and obtained the area under curve (AUC) with accuracy, sensitivity and specificity. RESULTS: The incidence of stillbirth was 2.5%. Predictors of stillbirth were history of abortion (aOR = 3.07, 95% CI 1.11-8.05, p = 0.0243), bilateral end-diastolic notch (aOR = 3.51, 95% CI 1.13-9.92, p = 0.0209), personal history of preeclampsia (aOR = 5.18, 95% CI 0.60-30.66, p = 0.0916), and haemoglobin 9.5 - 12.1 g/dL (aOR = 0.33, 95% CI 0.11-0.93, p = 0.0375). The models' AUC was 75.0% with 68.1% accuracy, 69.1% sensitivity and 67.1% specificity. CONCLUSION: Risk factors for stillbirth include history of abortion and bilateral end-diastolic notch, while haemoglobin of 9.5-12.1 g/dL is protective.

Antimicrobial Bioactivity and GC-MS Analysis of Different Extracts of Corchorus olitorius L Leaves.

Results: Crude extracts of Corchorus olitorius L leaves and their TLC-separated components demonstrated bioactivity against Staphylococcus aureus (14 mm), Streptococcus pneumoniae (16 mm), and Escherichia coli (11 mm) but neither against Candida albicans nor Mycobacteria tuberculosis. However, the overall zones of inhibition were smaller compared to the positive control (≥18 mm). GC-MS analysis of the active components revealed the presence of methyl esters. Conclusion: Corchorus olitorius L is bioactive against both Gram-negative and Gram-positive bacteria but neither against fungi nor mycobacteria. The bioactivity is attributable to the presence of methyl esters. Since methyl esters already have proven bioactivity in some studies, they could be further studied and optimized for possible pharmaceutical use. Further, to provide a more comprehensive antimicrobial spectrum of Corchorus olitorius L in Uganda, purified active components could be investigated using a wider range of organisms.

Phytochemical Analysis, Acute Toxicity, as well as Antihyperglycemic and Antidiabetic Activities of Corchorus olitorius L. Leaf Extracts.

Backgroundand Aim. Diabetes mellitus is a metabolic disorder that has no known cure with continuous endeavors to find a therapy for the condition. According to some studies, traditional leafy vegetables could prevent and manage diabetes by modifying the carbohydrate and lipid metabolism. In this study, a phytochemical analysis, acute toxicity, as well as antihyperglycemic and antidiabetic activity testing of the methanolic, diethyl ether, and aqueous leaf extracts of Corchorus olitorius L. was performed. Materials and Methods. Methanolic, diethyl ether, and aqueous leaf extracts of Corchorus olitorius L. were prepared by serial extraction. Phytochemical analysis was performed following standard methods. 52 mice were separated into 13 groups (A-M) of 4 and received extracts' doses ranging from 1000 mg/kg to 5000 mg/kg for the acute toxicity testing. For the antihyperglycemic and antidiabetic activities testing, 48 rats were divided into 8 groups of 6 and received 500 mg/kg of each extract. 10 mg/kg of glibenclamide and distilled water were used as controls. Data were analyzed using Prism GraphPad version 8.0.2 (263). Results. Phytochemical analysis revealed the presence of alkaloids, reducing sugars, saponins, and terpenoids. There were no acute toxicity signs observed in this study. Corchorus olitorius L. extracts demonstrated moderate antihyperglycemic and antidiabetic activities. The methanolic extract exhibited the highest degree of antihyperglycemic activity. However, there was no statistically significant difference between the extracts and the negative control (p > 0.05), but with glibenclamide (p < 0.01). Conclusion. Corchorus olitorius L. is a safe and potential postprandial antidiabetic vegetable that could minimize the rise in blood glucose after a meal. We therefore recommend further investigations into the antidiabetic properties of the vegetable using purified extracts.

Traditional Medicinal Vegetables in Northern Uganda: An Ethnobotanical Survey.

BACKGROUND: A wide range of indigenous vegetables grow in Uganda especially during rainy seasons but scarcely during droughts, except those that are commercially grown. Although a number of these vegetables have medicinal values, they have not been satisfactorily studied besides conservation. Therefore, we conducted a cross-sectional ethnobotanical survey in Northern Uganda in order to document traditional medicinal vegetables and their uses. METHODS: Qualitative and quantitative approaches of data collection and analysis were employed using semistructured, interviewer-administered questionnaires as well as key informant interviews following international ethical codes. Fidelity levels and informant consensus factors were also calculated. RESULTS: 13 traditional vegetables belonging to 10 families were reported to serve as folk medicines. The most dominant families were Fabaceae (23.08%) and Solanaceae (15.38%). The most often used vegetables were Corchorus spp., Hibiscus spp., and Asystasiagangeticafor musculoskeletal (51%), gastrointestinal (34.3%), and malaria (31.8%). The vegetables were cultivated in the backyard and the leaves stewed for the different ailments. The informant consensus factor was the highest for Corchorus spp., in the treatment of joint pain/stiffness (0.92-1) while the highest fidelity level was (60.42%) for Amaranthus spp., in the management of anemia. CONCLUSIONS: Northern Uganda has numerous traditional vegetables with medicinal benefits. Diseases treated range from gastrointestinal to reproductive through musculoskeletal abnormalities. The community obtains vegetable leaves from the backyard and stews them regularly for the medicinal purposes with no specific dosage. Therefore, we recommend studies to verify in laboratory models the efficacy of these vegetables and standardize the dosages.

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.

CYP2B6 genotype-based efavirenz dose recommendations during rifampicin-based antituberculosis cotreatment for a sub-Saharan Africa population.

AIM: To assess genotype effect on efavirenz (EFV) pharmacokinetics, treatment outcomes and provide genotype-based EFV doses recommendations during for tuberculosis (TB)-HIV-1 cotreatment. MATERIALS & METHODS: EFV concentrations from 158 HIV-TB co-infected patients treated with EFV/lamivudine/zidovidine and rifampicin were analyzed. Genotype and CD4 and viral load data were analyzed using a population PK model. RESULTS: Simulated AUCs for 600 mg EFV dose were 1.2- and 2.4-times greater than the product label for Ugandans in general and CYP2B6*6/*6 genotypes respectively. EFV daily doses of 450 and 250 mg for Ugandans and CYP2B6*6/*6 genotypes, respectively, yielded simulated exposures comparable to the product label. CONCLUSIONS: Around 450 and 250 mg daily doses might meet EFV dosing needs of HIV-TB infected Ugandans in general and CYP2B6*6/*6 genotypes, respectively.

Prevalence and predictors of prior antibacterial use among patients presenting to hospitals in Northern Uganda.

BACKGROUND: Human antibacterial exposure occur in different ways including consumption of animal and agricultural products as well as use of prescribed and non-prescribed agents. We estimated the prevalence and explored the predictors of antibacterial use among patients presenting to hospitals in northern Uganda. METHODS: Four hundred fifty (450) patients were randomly selected and antibacterial use prior to hospital visit measured using a questionnaire and urine antibacterial activity assay. Urine antibacterial bioassays were performed using American type culture collections of Escherichia coli, Bacillus subtilis and Streptococcus pyogenes. Data were analysed using STATA 12.0 at 95% confidence level. RESULTS: Of 450 patients interviewed, 62.2% had used antibacterial agents. Urine antibacterial activity was detected in 30.4% of the samples tested. Of the 85 patients who reported not taking any antibacterial at home, 16 (18.8%) had urine with antibacterial activity. Most test bacteria, E. coli (74.5%), B. subtilis (72.6%) and S. pyogens (86.7%) were sensitive to urine of patients who reported using antibacterial drugs before hospital visit. From the interview, metronidazole 15.6% (70/450), amoxicillin 12% (54/450), and ciprofloxacin 10.4% (47/450) were the most used antibacterial agents. Patient age (OR, 2.45: 95% CI: 1.02-5.91: P = 0.024), time-lag between last drug intake and hospital visit (OR: 3.18: 95% CI: 1.44-7.0: P < 0.0001), and time-lag between illness onset and hospital visit (OR: 1.89: 95% CI: 0.38-5.1: P = 0.027) predicted the use of antibacterial agents before hospital visit. DISCUSSION: Community antibacterial use continues to take place in an unregulated manner. In addition, physiciansrarely seek to ascertain prior use of antibacterial agents among patients presenting to hospitals. This couldhave a bearing on patient treatment outcomes. CONCLUSION: Knowledge of prior antibacterial use among patients presenting to hospitals is useful to physicians in ensuring antibacterial stewardship.

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.

Explaining the slow transition of child-appropriate dosage formulations from the global to national level in the context of Uganda: a qualitative study.

BACKGROUND: In 2007, the Sixtieth World Health Assembly (WHA) passed a resolution entitled "Better medicines for children" and subsequently the World Health Organization (WHO) recommended the inclusion of child-appropriate dosage formulations in the essential medicines lists of member countries. However, child-appropriate dosage formulations are not highlighted in the Essential Medicines and Health Supplies List of Uganda (EMHSLU) 2012 and they are still limited in availability in public health facilities. Several stakeholders influenced the status of child-appropriate dosage formulations in the EMHSLU 2012. OBJECTIVE: To explore stakeholders' views about the relevance of the globally recommended child-appropriate dosage formulations in the context of Uganda. METHODS: The findings derive from thirty three in-depth interviews with stakeholder representatives and the results of a follow up validation meeting where preliminary findings were shared with stakeholders. Policy analysis and policy transfer theories were used to guide a deductive analysis for manifest and latent content. RESULTS: According to stakeholders, the transition to the globally recommended child-appropriate dosage formulations has been slow in Uganda due to a number of factors. These factors include resource constraints at the global and national levels, lack of Ministry of Health (MOH) formal commitment to the adoption of the child-appropriate dosage formulations policy and a lack of consensus between those who advocated for the availability of liquid oral dosage formulations for easy administration and effectiveness and those who were more convinced by economic arguments and preferred the procurement of solid oral dosage formulations intended for adults. CONCLUSIONS: The global policy for child-appropriate dosage formulations still remains to be implemented in Uganda and other low income countries. This has been due to lack of resources that hindered formal transfer of the policy from the global to the local level. To achieve this transfer there is a need for resource mobilisation at both the international and local levels, together with the revitalisation of UMTAC to enable it to take on a leadership role of the coalitions supporting child-appropriate dosage formulations.

Availability and utilization of the WHO recommended priority lifesaving medicines for under five-year old children in public health facilities in Uganda: a cross-sectional survey.

OBJECTIVES: To explore the availability and utilization of the World Health Organization (WHO) recommended priority life-saving medicines for children under five in public health facilities in Uganda. METHODS: We conducted a cross sectional survey in 32 lower level public facilities in Jinja district of Uganda. A proportionate number of facilities were randomly selected in each stratum following a hierarchy of Health Centers (HC) defined according to the level of care they provide: 17 HC IIs, 10 HC IIIs and 5 HC IVs. In the facilities, we verified the availability of the WHO recommended priority medicines for diarrhea, sepsis, pneumonia and malaria. 81 health workers from the facilities reported what they prescribed for children with the above diseases. RESULTS: Oral rehydration salt (ORS) and zinc sulphate dispersible tablets for diarrhea were available in all HC IIs and IIIs and in only 60% of HC IVs. Procaine benzyl penicillin injection powder for treatment of sepsis was available in the majority of all HCs with: 100% of HC of IVs, 83% of HC IIIs and 82% of HC IIs. Medicines for pneumonia were limited across all the HCs with: Amoxicillin dispersible tablets in only 30% of the HC IIs and 40% of the HC IVs. The most uncommon were child-friendly priority medicines for malaria with: Artesunate injection in only 6% of HC IIs, 14% of HC IIIs and 20% of HC IVs; Artemether lumefantrine dispersible tablets and rectal artesunate were missing in all the 32 HCs. Less than a third of the health workers reported prescribing zinc sulphate and ORS for diarrhea, 86% reported procaine benzyl penicillin injection powder for sepsis, and 57% reported amoxicillin dispersible tablets for pneumonia. None reported prescribing Artemether lumefantrine dispersible tablets and rectal artesunate for malaria. CONCLUSIONS: There is low availability and utilization of life-saving priority medicines for pneumonia and malaria in public health facilities in Uganda. However, the priority medicines for diarrhea and sepsis are available and highly prescribed by the health workers.

The "child size medicines" concept: policy provisions in Uganda.

BACKGROUND: In 2007, the World Health Organization (WHO) launched the 'make medicines child size' (MMCS) campaign by urging countries to prioritize procurement of medicines with appropriate strengths for children's age and weight and, in child-friendly formulations of rectal and flexible oral solid formulations. This study examined policy provisions for MMCS recommendations in Uganda. METHODS: This was an in-depth case study of the Ugandan health policy documents to assess provisions for MMCS recommendations in respect to oral and rectal medicine formulations for malaria, pneumonia and diarrhea, the major causes of morbidity and mortality among children in Uganda- diseases that were also emphasized in the MMCS campaign. Asthma and epilepsy were included as conditions that require long term care. Schistomiasis was included as a neglected tropical disease. Content analysis was used to assess evidence of policy provisions for the MMCS recommendations. RESULTS: For most medicines for the selected diseases, appropriate strength for children's age and weight was addressed especially in the EMHSLU 2012. However, policy documents neither referred to 'child size medicines' concept nor provided for flexible oral solid dosage formulations like dispersible tablets, pellets and granules- indicating limited adherence to MMCS recommendations. Some of the medicines recommended in the clinical guidelines as first line treatment for malaria and pneumonia among children were not evidence-based. CONCLUSION: The Ugandan health policy documents reflected limited adherence to the MMCS recommendations. This and failure to use evidence based medicines may result into treatment failure and or death. A revision of the current policies and guidelines to better reflect 'child size', child appropriate and evidence based medicines for children is recommended.

CYP2B6 genotype, but not rifampicin-based anti-TB cotreatments, explains variability in long-term efavirenz plasma exposure.

AIM: We investigated the effects of rifampicin-based anti-TB treatment on plasma efavirenz exposure and the implications of CYP2B6 genotype. PATIENTS & METHODS: Antiretroviral therapy-naive Ugandan HIV patients without (n = 157) or with TB coinfection (n = 106) were enrolled and treated with efavirenz-based highly active antiretroviral therapy alone or with rifampicin-based anti-TB therapy, respectively. Efavirenz plasma concentration was determined on day 3 and weeks 1, 2, 8, 12, 16, 20, 24, 28 and 32. RESULTS: Rifampicin-based anti-TB cotreatment reduced plasma efavirenz exposure during the first 2 weeks (p < 0.05), but no significant effect was observed afterwards. Although not significant, rifampicin-based anti-TB cotreatment inconsistently increased efavirenz exposure over time, which was reduced immediately after completing anti-TB therapy. CYP2B6*6, *11 and ABCB1 c.4036A>G genotypes were significant predictors of efavirenz plasma exposure. CONCLUSION: Plasma efavirenz exposure is mainly influenced by CYP2B6 genotype, but not by rifampicin cotreatment. Therefore, no efavirenz dosage adjustment during rifampicin cotreatment is required in Ugandans.

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.

Patterns and predictors of self-medication in northern Uganda.

Self-medication with antimicrobial agents is a common form of self-care among patients globally with the prevalence and nature differing from country to country. Here we assessed the prevalence and predictors of antimicrobial self-medication in post-conflict northern Uganda. A cross-sectional study was carried out using structured interviews on 892 adult (≥18 years) participants. Information on drug name, prescriber, source, cost, quantity of drug obtained, and drug use was collected. Households were randomly selected using multistage cluster sampling method. One respondent who reported having an illness within three months in each household was recruited. In each household, information was obtained from only one adult individual. Data was analyzed using STATA at 95% level of significance. The study found that a high proportion (75.7%) of the respondents practiced antimicrobial self-medication. Fever, headache, lack of appetite and body weakness were the disease symptoms most treated through self-medication (30.3%). The commonly self-medicated antimicrobials were coartem (27.3%), amoxicillin (21.7%), metronidazole (12.3%), and cotrimoxazole (11.6%). Drug use among respondents was mainly initiated by self-prescription (46.5%) and drug shop attendants (57.6%). On average, participants obtained 13.9±8.8 (95%CI: 12.6-13.8) tablets/capsules of antimicrobial drugs from drug shops and drugs were used for an average of 3.7±2.8 days (95%CI: 3.3-3.5). Over half (68.2%) of the respondents would recommend self-medication to another sick person. A high proportion (76%) of respondents reported that antimicrobial self-medication had associated risks such as wastage of money (42.1%), drug resistance (33.2%), and masking symptoms of underlying disease (15.5%). Predictors of self-medication with antimicrobial agents included gender, drug knowledge, drug leaflets, advice from friends, previous experience, long waiting time, and distance to the health facility. Despite knowledge of associated risks, use of self-medication with antimicrobial drugs in management of disease symptoms is a common practice in post-conflict northern Uganda.

Pharmacogenetic-based efavirenz dose modification: suggestions for an African population and the different CYP2B6 genotypes.

BACKGROUND: Pharmacogenetics contributes to inter-individual variability in pharmacokinetics (PK) of efavirenz (EFV), leading to variations in both efficacy and toxicity. The purpose of this study was to assess the effect of genetic factors on EFV pharmacokinetics, treatment outcomes and genotype based EFV dose recommendations for adult HIV-1 infected Ugandans. METHODS: In total, 556 steady-state plasma EFV concentrations from 99 HIV infected patients (64 female) treated with EFV/lamivudine/zidovidine were analyzed. Patient genotypes for CYP2B6 (*6 & *11), CYP3A5 (*3,*6 & *7) and ABCB1 c.4046A>G, baseline biochemistries and CD4 and viral load change from baseline were determined. A one-compartment population PK model with first-order absorption (NONMEM) was used to estimate genotype effects on EFV pharmacokinetics. PK simulations were performed based upon population genotype frequencies. Predicted AUCs were compared between the product label and simulations for doses of 300 mg, 450 mg, and 600 mg. RESULTS: EFV apparent clearance (CL/F) was 2.2 and 1.74 fold higher in CYP2B6*6 (*1/*1) and CYP2B6*6 (*1/*6) compared CYP2B6*6 (*6/*6) carriers, while a 22% increase in F1 was observed for carriers of ABCB1 c.4046A>G variant allele. Higher mean AUC was attained in CYP2B6 *6/*6 genotypes compared to CYP2B6 *1/*1 (p<0.0001). Simulation based AUCs for 600 mg doses were 1.25 and 2.10 times the product label mean AUC for the Ugandan population in general and CYP2B6*6/*6 genotypes respectively. Simulated exposures for EFV daily doses of 300 mg and 450 mg are comparable to the product label. Viral load fell precipitously on treatment, with only six patients having HIV RNA >40 copies/mL after 84 days of treatment. No trend with exposure was noted for these six patients. CONCLUSION: Results of this study suggest that daily doses of 450 mg and 300 mg might meet the EFV treatment needs of HIV-1 infected Ugandans in general and individuals homozygous for CYP2B6*6 mutation, respectively.

Chronic ethanol use in alcoholic beverages by HIV-infected patients affects the therapeutic window of stavudine, lamivudine and nevirapine during the 9-month follow-up period: using chronic alcohol-use biomarkers.

Abstract Background: Chronic ethanol use is a global problem including among HIV-infected patients on stavudine/lamivudine/nevirapine (d4T/3TC/NVP) regimen. The study determined the effect of chronic ethanol use on the therapeutic window of d4T, 3TC and NVP in HIV-infected patients using alcohol-use biomarkers to screen patients for chronic ethanol use. Methods: A case-control study using repeated measures design with serial measurements was used to quantify drugs in plasma. The WHO alcohol use disorder identification test (AUDIT) tool was initially used to screen patients for chronic alcohol use, and then they were further sorted using alcohol-use bioamarkers (γ-glutamyl transferase ≥55.0 IU; mean corpuscular volume, ≥96 fl, aspartate amino transferase/alanine aminotransferase ratio ≥2.0 value). A total of 41 patients (26 in the alcohol group and 15 in the control group) were followed up for 9 months with blood sampling done at 3-month intervals. Plasma drug concentrations were quantified using a Shimadzu Class-VP™ HPLC data system version 6.1. Data was analyzed using SAS 2003 version 9.1 statistical package with repeated measures fixed model. Means were compared using Student's t-test. Results: The mean steady-state plasma drug concentrations of d4T and 3TC in the alcohol group were lower than that in the control group during the 9-month period of follow-up. For 3TC, there was a statistical difference in the mean steady-state plasma drug concentrations between the alcohol group and the control group (p≤0.05) in the 6- and 9-month period of follow-up. For NVP, in both groups they were within the reference ranges, although the drug plasma concentrations were higher in the alcohol group compared to the control group and were statistically significant (p<0.05) in 0, 3 and 6 months of follow-up. Conclusions: Chronic ethanol use by HIV-infected patients reduced the therapeutic steady-state plasma drug concentrations of d4T and 3TC and increased the NVP drug concentrations in the HIV-infected patients.

Influence of efavirenz pharmacokinetics and pharmacogenetics on neuropsychological disorders in Ugandan HIV-positive patients with or without tuberculosis: a prospective cohort study.

BACKGROUND: HIV infection, anti-tuberculosis and efavirenz therapy are associated with neuropsychological effects. We evaluated the influence of rifampicin cotreatment, efavirenz pharmacokinetics and pharmacogenetics on neuropsychiatric disorders in Ugandan HIV patients with or without tuberculosis coinfection. METHODS: 197 treatment naïve Ugandan HIV patients, of whom 138 were TB co-infected, enrolled prospectively and received efavirenz based HAART. TB-HIV confected patients received concomitant rifampicin based anti-TB therapy. Genotypes for CYP2B6 (*6, *11), CYP3A5 (*3, *6, *7), ABCB1 (c.3435C>T and c.4036 A/G rs3842), CYP2A6 (*9, *17) and NR1I3 rs3003596 T/C were determined. Efavirenz plasma concentrations were serially quantified at 3rd day, 1st, 2nd, 4th, 6th, 8th and 12th weeks during therapy. Efavirenz neuropsychiatric symptoms were evaluated in terms of sleep disorders, hallucinations and cognitive effects at baseline, at two and twelve weeks of efavirenz treatment using a modified Mini Mental State Examination (MMSE) score. RESULTS: During the first twelve weeks of ART, 73.6% of the patients experienced at least one efavirenz related neuropsychiatric symptom. Commonest symptoms experienced were sleep disorders 60.5% (n=124) and hallucination 30.7% (n=63). Neuropsychiatric symptoms during HAART were significantly predicted by efavirenz plasma concentrations consistently. Rifampicin cotreatment reduced plasma efavirenz concentrations significantly only during the first week but not afterwards. There was no significant difference in the incidence of neuropsychiatric symptoms between patients receiving efavirenz with or without rifampicin cotreatment. CYP2B6*6 and ABCB1 c.4036 A/G genotype significantly predicted efavirenz concentrations. The tendency of CYP2B6*6 genotype association with higher incidence of having vivid dream (p=0.05), insomnia (p=0.19) and tactile hallucination (p=0.09) was observed mainly at week-2. CONCLUSIONS: Efavirenz related neuropsychiatric symptoms are common among Ugandan HIV patients receiving ART and is mainly predicted by higher efavirenz plasma concentrations and CYP2B6 genotype but not by rifampicin based anti-TB co-treatment.