Jasper Ogwal-Okeng

Medicinal plants used by traditional medicine practitioners for the treatment of HIV/AIDS and related conditions in Uganda

INTRODUCTION AND OBJECTIVESnIn Uganda, there are over one million people with HIV/AIDS. When advanced, this disease is characterized by life-threatening opportunistic infections. As the formal health sector struggles to confront this epidemic, new medicines from traditional sources are needed to complement control efforts. This study was conducted to document herbal medicines used in the treatment of HIV/AIDS and related opportunistic infections, and to document the existing knowledge, attitudes and practices related to HIV/AIDS recognition, control and treatment in Sembabule, Kamuli, Kabale and Gulu districts in Uganda.nnnMETHODSnIn this study, 25 traditional medicine practitioners (TMPs) were interviewed using structured questionnaires.nnnRESULTSnThe TMPs could recognize important signs and symptoms of HIV/AIDS and its associated opportunistic infections. The majority of practitioners treated patients who were already receiving allopathic medicines including antiretroviral drugs (ARVs) prescribed by allopathic practitioners. There were 103 species of medicinal plants identified in this survey. Priority plants identified include Aloe spp., Erythrina abyssinica, Sarcocephalus latifolius, Psorospermum febrifugum, Mangifera indica and Warburgia salutaris. There was low consensus among TMPs on the plants used. Decoctions of multiple plant species were commonly used except in Gulu where mono-preparations were common. Plant parts frequently used were leaves (33%), stem bark (23%) and root bark (18%). About 80% of preparations were administered orally in variable doses over varied time periods. The TMP had insufficient knowledge about packaging and preservation techniques.nnnCONCLUSIONSnNumerous medicinal plants for treatment of HIV/AIDS patients were identified in the four districts surveyed and the role of these plants in the management of opportunistic infections warrants further investigation as these plants may have a role in Ugandas public health approach to HIV/AIDS control.

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

BackgroundHIV 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.Methods197 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.ResultsDuring 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.ConclusionsEfavirenz 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.

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

BackgroundAntimicrobial 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.MethodsIn 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.ResultsA 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 %).ConclusionThe 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.

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.

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.

Factors predicting home storage of medicines in Northern Uganda

BackgroundMedicines 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.MethodA 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.ResultsOf 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 6u2009±u20095 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.ConclusionOver 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.

Steady-state pharmacokinetics of lopinavir plus ritonavir when administered under different meal conditions in HIV-infected Ugandan adults.

Abstract:We investigated the effect of food on the steady-state pharmacokinetics of lopinavir and ritonavir in 12 Ugandan patients receiving lopinavir coformulated with ritonavir (LPV/r) tablets using a crossover design. Intensive pharmacokinetic sampling was performed 7 days apart after LPV/r dosing under moderate fat, high fat, and fasted meal conditions. Lopinavir and ritonavir concentrations were determined by liquid chromatography and tandem mass spectrometry. Compared with the fasted state, a high fat meal reduced lopinavir and ritonavir area under the curve by 14% and 29%, respectively. With a moderate fat meal, area under the curve for both drugs was similar to the fasted state.

The “child size medicines” concept: policy provisions in Uganda

BackgroundIn 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.MethodsThis 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.ResultsFor 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.ConclusionThe 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.

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

BackgroundHuman 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.MethodsFour 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 95xa0% confidence level.ResultsOf 450 patients interviewed, 62.2xa0% had used antibacterial agents. Urine antibacterial activity was detected in 30.4xa0% of the samples tested. Of the 85 patients who reported not taking any antibacterial at home, 16 (18.8xa0%) had urine with antibacterial activity. Most test bacteria, E. coli (74.5xa0%), B. subtilis (72.6xa0%) and S. pyogens (86.7xa0%) were sensitive to urine of patients who reported using antibacterial drugs before hospital visit. From the interview, metronidazole 15.6xa0% (70/450), amoxicillin 12xa0% (54/450), and ciprofloxacin 10.4xa0% (47/450) were the most used antibacterial agents. Patient age (OR, 2.45: 95xa0% CI: 1.02–5.91: Pu2009=u20090.024), time-lag between last drug intake and hospital visit (OR: 3.18: 95xa0% CI: 1.44–7.0: Pu2009<u20090.0001), and time-lag between illness onset and hospital visit (OR: 1.89: 95xa0% CI: 0.38–5.1: Pu2009=u20090.027) predicted the use of antibacterial agents before hospital visit.DiscussionCommunity 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.ConclusionKnowledge of prior antibacterial use among patients presenting to hospitals is useful to physicians in ensuring antibacterial stewardship.

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

ObjectivesTo 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.MethodsWe 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.ResultsOral 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.ConclusionsThere 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.