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Traditional herbal remedies for managing COVID-19 major symptoms: A case study of Kole district, Northern Uganda
(TMR Pharmacology Research, 2021) Nakaziba, Rebecca; Anyolitho, Maxson Kenneth; Kabunga, Amir
Background: Today, the world is battling COVID-19 which has claimed millions of lives within a short period. As biotechnological research is in progress, it’s expedient to explore alternative sources of medication. Exploring plants that have been used in the management of COVID-19 related symptoms for ages may unveil a potential treatment option for this pestilence. We, therefore, conducted a study in Kole district, Northern Uganda to document the plants that are used in the management of the four key COVID-19 related symptoms including flue, cough, sore throat, and difficulty in breathing. Materials and Methods: We employed a cross-sectional quantitative survey design. We used stratified sampling to select 50 participants from each of the five sub-counties in the district, and convenience sampling to select a total of 250 participants and administered interviewer-administered questionnaires. Results: We identified over 50 herbs that are used in the treatment of COVID-19 related symptoms. However, we were able to report on the fourteen most common ones that belonged to 12 families in this paper. Clematis hirsute Perr. & Guill, (68.0%) and Citrus limon burm. F. (30.8%); Eucalyptus grandis M., (49.2%) and Zingibar officinalis, (28.0%); Conyza floribunda H.B.K. (26.4%) and Allium sativum A. (23.6%); Capparis tomentosa Lam. (19.4%) and Acacia hockii De Wild, (17.4%): for the treatment of flu, cough, sore throat and breathing difficulties respectively. Different plant parts of the diverse plant species were used in treating the symptoms. For Clematis hirsute Perr. & Guill, all plant parts were used differently to treat each of the 4 symptoms. Conclusion: Kole district possesses a multitude of herbs with the potential of treating COVID-19 symptoms. There is a need for further pharmacological investigations to validate their activity and possible development for clinical use in the management of COVID-19.
Intimate partner violence among pregnant teenagers in Lira district, northern Uganda: a cross-sectional study
(African Journal of Midwifery and Women's Health, 2020) Auma, Anna Grace; Ayebare, Elizabeth; Olwit, Connie; Ndeezi, Grace; Nankabirwa, Victoria; Tumwine, -James K
Background/aims Intimate partner violence during pregnancy is associated with adverse health outcomes for mothers and their unborn babies. Whereas the literature on intimate partner violence in the general population is extensive, little is known about this type of violence among pregnant teenagers, especially in resource-limited settings. This study aimed to determine the prevalence and factors associated with intimate partner violence among pregnant teenagers attending antenatal care clinics in Lira District, northern Uganda. Methods This was a cross-sectional study of 310 pregnant teenagers attending antenatal care clinics at the Lira Regional Referral Hospital and Ogur Health Center IV. Eligible teenagers were recruited consecutively until the required sample size was accrued. Data were collected using a structured questionnaire. Intimate partner violence was determined using the Revised Conflict Tactile Scale 2. Logistic regression analysis was performed to identify factors associated with violence during pregnancy, while considering potential confounding factors. Results The overall prevalence of intimate partner violence among pregnant teenagers was 40.6%. The prevalence of psychological violence was 37.1%, sexual assault was 29%, and physical violence was 24.8%. Partner alcohol intake (odds ratio=5.00, P=0.000); polygamy (odds ratio=2.80, P=0.001) and the inability of the teenage mother to make major decisions in the home (odds ratio=2.42, P=0.006) were independently associated with intimate partner violence during pregnancy. Conclusions Approximately 4 in 10 pregnant teenagers in Lira district, northern Uganda experienced intimate partner violence. This is higher than has been reported in the general population of pregnant women in Uganda. Intimate partner violence screening and counselling should be part of the routine antenatal care package.
Traditional Medicinal Vegetables in Northern Uganda: An Ethnobotanical Survey
(International Journal of Food Science, 2021) Nakaziba, Rebecca; Anyolitho, Maxson Kenneth; Amanya, Sharon Bright; Sesaazi, Crispin Duncan; Byarugaba, Frederick; Ogwal-Okeng, Jasper; Alele, Paul E.
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
Chronic alcohol use reduces CD4+counts in HIV/AIDS patients on d4T/3TC/NVP treatment regimen using WHO AUDIT tool and alcohol-use biomarkers
(Research & Reviews in BioSciences, 2014) Bbosa, Godfrey S.; Kyegombe, David B.; Anokbonggo, William W.; Mugisha, Apollo; Ogwal-Okeng, Jasper
Alcohol is one of the most abused drugs worldwide by people of different socio-economic status, age groups and including the HIV/AIDS patient on treatment. It is reward drug and a CNS depressant especially at high doses. The study investigated effect of chronic alcohol exposure by HIV/ AIDS patients on d4T/3TC/NVP regimen on CD4+counts inUganda using WHO AUDIT tool and chronic alcohol-use biomarkers. A longitudinal cohort using repeated measures design with serial measurements model was used. TheWHOAUDIT toolwas used to screen patients on stavudine (d4T) 30mg, lamivudine (3TC) 150mg and nevirapine (NVP) 200mg for chronic alcohol use.Atotal of 41 patients (20 alcohol group and 21 control group) were screened for chronic alcohol use. They were followed up for 9 months with blood sampling done at 3 month intervals. CD4+ count was determined using Facscalibur Flow Cytometer equipment. Results were then sorted by alcohol-use biomarkers (GGT, MCV and AST/ALT ratio). Data was analysed using SAS 2003 version 9.1 statistical package with repeatedmeasures fixedmodel and themeanswere compared using student t-test. Themean CD4+ count in all groups were lower than reference ranges at baseline and gradually increased at 3, 6 and 9 month of follow up. The mean CD4+ count in control group were higher in the control group as compared to the chronic alcohol use group in both WHO AUDIT tool group and chronic alcohol-use biomarkers group though there was no significant difference (p>0.05). Chronic alcohol use slightly lowers CD4+ cell count in HIV/AIDS patients on d4T/3TC/NVP treatment regimen.
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
(Journal of Basic and Clinical Physiology and Pharmacology, 2013) Bbosa, Godfrey S.; Kyegombe, David B.; Anokbonggo, William W.; Ogwal-Okeng, Jasper; Musoke, David; Odda, John; Lubega, Aloysius; Ntale, Muhammad
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.
Artemisia Annua L. Infusion Consumed Once a Week Reduces Risk of Multiple Episodes of Malaria: A Randomised Trial in a Ugandan Community
(Tropical Journal of Pharmaceutical Research, 2012) Ogwang, Patrick E; Ogwal-Okeng, Jasper; Kasasa, Simon; Olila, Deogratius; Ejobi, Francis; Kabasa, David; Obua, Celestino
Purpose: To evaluate the protective effect of Artemisia annua infusion against malaria in a community that uses it as herbal ‘tea’ for malaria prevention. Methods: 132 flower farm workers who met the study inclusion criteria and were not yet using A. annua infusion were randomized either to A. annua or placebo groups in the ratio of 1:1. Treatments were administered once a week under direct observation to participants. Malaria episodes were documented over a 9-month period while adverse effects were documented over 12 months. Results: A. annua herbal ‘tea’ significantly reduced the risk of suffering more than one episode of malaria in nine months by 55 % (12/67 vs 26/65, p = 0.005 No participant experienced any serious adverse effect although bitter taste was the most common side effect of the infusion. Conclusion: Artemisia annua infusion consumed once a week was effective in preventing multiple episodes of malaria in humans living in malaria endemic areas. However, its bitter taste and the risk of development of malaria parasite resistance to the artemisinin contained in it remain major challenges for its use in the mass control of malaria.
Anti-Plasmodium falciparum activity of Aloe dawei and Justicia betonica
(African Journal of Pharmacy and Pharmacology, 2013) Bbosa, Godfrey S.; Kyegombe, David B.; Lubega, Aloysius; Musisi, Nathan; Ogwal-Okeng, Jasper; Odyek, Olwa
Malaria is a fatal disease caused by different Plasmodium species of parasites and has remained the major killer of humans worldwide especially the children under five years of age and pregnant women. In this study, the anti-Plasmodia activities of the crude leaf ether extracts of Aloe dawei (AD) and Justicia betonica (JB) on Plasmodium falciparum were investigated, with chloroquine diphosphate as a positive control. The results showed that ether extracts of JB had EC50 of 13.36 (95% CI: 8.032 to 22.23) μg/ml and AD had 7.965 (95% CI: 3.557 to 17.84) μg/ml. The chloroquine diphosphate had EC50 of 24.86 (95% CI: 9.239 to 66.89) μg/ml. The qualitative phytochemical analysis of the ether extract showed that JB contains steroids and triterpenoids, alkaloids and saponins while AD contained steroids and triterpenoids, anthraquinolones, alkaloids and saponins. The results provides evidence that JB and AD contain compounds with anti-P. falciparum activity and hence their use by the traditional herbalist and local communities in treatment of malaria.
Antiplasmodial activity of extracts of selected medicinal plants used by local communities in western Uganda for treatment of malaria
(African Journal of Ecology, 2007) Katuura, Esther; Waako, Paul; Tabuti, John R. S.; Bukenya-Ziraba, Remigius; Ogwal-Okeng, Jasper
This study investigated the antiplasmodial activity of ten medicinal plants used to treat malaria in Southwestern Uganda. The study plants were Bothlioclines longpipes (Olive and Hiern), N.E.Br., Toddalia asiatica (L.) Lam., Maesa lanceolata Forssk., Indigofera emerginella steud. Ex A. Rich., Lantana trifolia L., Vernonia lasiopus O. Hoffm., Trimmeria bakeri Gilg., Rhus natalensis Bernh. ex. Krauss Erythrophleum pyrifolia and Conyza sp. Dry powdered plant material was extracted by sequential cold maceration using petroleum ether, chloroform and ethanol solvents respectively. Extracts were subjected to in vitro antiplasmodial screening against wild strains of Plasmodium falciparum using the nitro-tetrazolium blue-based lactate dehydrogenase assay. The chloroform extract of M. lanceolata (EC50 1.60 lg ml)1.), showed the highest antiplasmodial activity followed by R. natalensis (EC50 1.80 lg ml)1). Other extracts with significant activity were the chloroform leaf extract of Bothriocline longipes (EC50 3.66 lg ml)1) and the petroleum ether root extract of T. bakeri (EC50 3.955 lg ml)1).
Medical Foods and Infant Formulas
(Springer, 2020) Mtewa, Andrew G.; Kasali, Mushagalusa F.; Bekele, Tamirat; Obura, Bonniface
Medical foods are foods that are formulated specifically to help in the management of diseases with particular dietary needs hardly met singly by normal diet. They are taken under medical prescription or supervision. On the other hand, infant formulas are basically foods designed for baby consumption that are intended for nutritive purposes. Some medical foods can also be designed as infant formula for ease of administration to babies. The most common types of medical foods are Ready-to-Use-Foods (RUFs) which are fortified to manage health complications, whist still maintaining high quality and safety standards. They can be used to prevent the development and/or progression of diseases. These foods need to have a scientifically determined shelf-life with a traceable trail of clinical trials as specified by international foods and health guidelines and regulations. This chapter explores the general outlook of medical foods and infant formulas including threats and future opportunities they present.
Off-label antibiotic use among paediatric in-patients: a mixed-method prospective study at a tertiary hospital in southwestern Uganda
(International Journal of Clinical Pharmacy, 2020) Obura, Bonniface; Obua, Celestino
Background The off-label use of drugs to treat children is a global practice attributed to the traditional exclusion of children from clinical trials mainly due to practical and ethical reasons. Off-label drug use carries both benefits and risks, but data regarding this use pattern are scanty in sub-Saharan Africa. Objective To determine the incidence and predictors of off-label antibiotic use in children less than 5 years admitted at Mbarara Regional Referral Hospital (MRRH) in southwestern Uganda. Setting A prospective drug utilisation study was conducted among in-patients at the Paediatric Ward of MRRH from May to June 2019. Methods Clinical records and treatment notes of all children aged 0 to 59 months with at least one antibiotic prescription during the admission period were reviewed and included for data collection. Key informant interviews were conducted with physicians attending to patients in the Paediatric Ward. Main outcome measure Off-label use and potential predictors of off-label antibiotic use. Results Of 427 children admitted to the Paediatric Ward, 165 (38.6%) received 366 antibiotic prescriptions. However, 359 prescriptions belonging to 162 patients were analyzed. Off-label prescriptions occurred in 18.9% (95% CI: 14.9–23.0) of antibiotic prescriptions. Two categories of off-label prescriptions were found: off-label frequency of administration (n = 55, 80.9%), and off-label doses (n = 13, 19.1%). Ceftriaxone was the most common antibiotic prescribed at off-label doses, (n = 6, 8.8%) while ampicillin was the most common antibiotic prescribed with an off-label frequency of administration, (n = 39, 57.3%). Infants (1–23 months) received the majority (47.1%) of off-label antibiotic prescriptions; neonates (0–28 days) received 27.9%, and children (24–59 months) received 25% of the prescriptions. Controlling for sex and disease severity, age category remained significantly associated with off-label antibiotic use on multivariate analysis. Conclusion Off-label frequency of administration was the major category of off-label drug use, while off-label dose was the minor category. Age was a significant factor for off-label antibiotic prescription, with infants receiving the highest number of off-label prescriptions. Attending physicians identified several justifiable circumstances that warrant off-label antibiotic use and support emerging “well-founded” off-label uses of antibiotics in different paediatric age groups
Antimicrobial activity and phytochemical fingerprints of five crude extracts obtained from indigenous medicinal plants of Uganda
(Research in Pharmaceutical Biotechnology, 2017) Katuura, Esther; Bbosa, Godfrey Sande; Waako, Paul; Ogwal-Okeng, Jasper
Five crude extracts from four Ugandan plants were screened in vitro for their antimicrobial activity and phytochemical composition. They included the chloroform extracts of Bothliocline longipes, Maesa lanceolata, Trimeria bakeri, Rhus natalensis and the petroleum ether extract of T. bakeri. The plant crude extracts were tested against Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 49619) and Entamoeba sp. Antimicrobial activities of the plants were determined by using the agar well diffusion and agar well dilution methods. The plant extracts showed activity against all the tested organisms with the zones of inhibition ranging from 4 to 19 mm. All the extracts inhibited the growth of S. aureus while the strongest activity was found for T. bakeri against S. aureus and Entamoeba sp. at 19 mm. Other plant extracts that induced strong antimicrobial activity were the chloroform extract of R. natalensis with an inhibition diameter of 13 mm against both S. aureas and P. aeruginosa and 9 mm diameter inhibition against E. coli. Only T. bakeri showed growth inhibition of S. aureus (4 mm). The minimum inhibitory concentration (MIC) was observed against S. aureus at 0.25 g/ml by the T. bakeri and B. longipes plant extracts. Sterol and triterpenes, fatty acids, flavanoids, coumarins and alkaloids were determined in T. bakeri, B. longipes, R. natalensis and M. lanceolata. The presence of these compounds indicates that the plants may contain an active compound or one that can be used as a template for the development of a new antimalarial or antibiotic medicine.
Antimalarial Activity of Aspilia pruliseta, a Medicinal Plant from Uganda
(Planta Medica : Journal of Medicinal Plant and Natural Product Research, 2010) Sebisubi, Fred Musoke; Odyek, Olwa; Anokbonggo, William Wilberforce; Ogwal-Okeng, Jasper; Carcache-Blanco, Esperanza J.; Ma, Cuiying; Orjala, Jimmy; Tan, Ghee T.
Aspilia prulisetaSchweinf. (Asteraceae) is a medicinal plant in-digenous to Uganda and the neighboring countries of East Africa.It has been used extensively by the rural population for the treat-ment of fevers and malaria. During the antimalarial evaluation ofthis plant, four nontoxic diterpenes were isolated that possessedmoderate activity against chloroquine-sensitive (D6) and chloro-quine-resistant (W2) clones ofPlasmodium falciparum, with IC50values ranging from 14 to 23 μM. These moderately active com-pounds included the previously undescribed diterpene,ent-15β-senecioyloxy-16,17-epoxy-kauran-18-oic acid that demonstrat-ed an IC50value of 23.4 μM against clone D6, but was devoid ofactivity against clone W2. Four additional diterpenes were ob-tained from the aerial parts ofA. pruliseta, but these known com-pounds were essentially inactive. The moderate activities of se-lect diterpenes ofA. prulisetacould account collectively for thehistorical and enduring use of this plant in traditional Africanmedicine.
Aflatoxins metabolism, effects on epigenetic mechanisms and their role in carcinogenesis
(Health, 2013) Bbosa, Godfrey S.; Kitya, David; odda, John; Ogwal-Okeng, Jasper
Chronic consumption of aflatoxin-contaminated foods is a global problem in both developing and developed countries especially where there is poor regulation of their levels in foods. In the body, aflatoxins (AFBs) mainly AFB1 are bio- transformed to various metabolites especially the active AFB1-exo-8,9-epoxide (AFBO). The AFB, AFBO and other metabolites interact with various biomolecules in the body including nu- cleic acids such as DNA and RNA and the vari- ous metabolic pathways such as protein syn- thesis, glycolytic pathway and electron trans- port chain involved in ATP production in body cells. The AFB interacts with DNA to form AFB- DNA adducts causing DNA breakages. The AFB and its metabolites induce the up regulation of nuclear receptors such as pregnane X receptor (PXR), constitutive androstane receptor (CAR), and aryl hydrocarbon receptor (AhR) through gene expression that regulates the metabolizing enzymes such as CYP450 involved in Phase I and Phase II metabolism of xenobiotics. AFB ac- tivates these nuclear receptors to produce the metabolizing enzymes. The AFB1 is metabolized in the body by cytochrome P450 (CYP450) enzyme isoforms such as CYP1A2, CYP1A2, CYP3A4/ CYP3A5, and CYP3A7 in fetus, glutathione S- transferase, aflatoxin B1-aldehyde reductase leading to reactive metabolites, some of which can be used as aflatoxin exposure biomarkers. These enzymes are involved in the Phase I and Phase II metabolic reactions of aflatoxins. The CYP1A2 is the principal metabolizer of aflatoxin at low concentrations while the reverse is true for CYP3A4. The accumulation of AFB and its metabolites in the body especially the AFB1-exo-8,9-epoxide depletes the glutathione (GSH) due to the formation of high amounts of epoxides and other reactive oxygen species (ROS). The AFB, AFB1-exo-8,9-epoxide and other metabo- lites also affect the epigenetic mechanisms in- cluding the DNA methylation, histone modifica-tions, maturation of miRNAs as well as the daily formation of single nucleotide polymorphism (SNP) where AFB exposure may facilitate the process and induces G:C to T:A transversions at the third base in codon 249 of TP53 causing p53 mutations reported in hepatocellular carcinoma (HCC). The changes in epigenetic mechanisms lead to either epigenetic inactivation or epige- netic derepression and all these affect the gene expression, cellular differentiation and growth. AFB also through epigenetic mechanisms pro- motes tumorigenesis, angiogenesis, invasion and metastasis in hepatocellular carcinoma. However, the formation of the small amounts of AFB1 from AFB2 is suspected to cause the carcinogenicity of AFB2 in humans and animals. Chronic afla- toxins exposure leads to formation of reactive AFBO metabolites in the body that could acti- vate and de-activates the various epigenetic me- chanisms leading to development of various cancers.
Acute toxicity effects of the methanolic extract of Fagara zanthoxyloides (Lam.) root-bark
(African Health Sciences, 2003) Ogwal-Okeng, Jasper; Obua, Celestino.; Anokbonggo, William W.
Background: Fagara zanthoxyloides is a well known medicinal plant in Uganda. It is used extensively in malaria and other infections. However nothing is known about its toxicity. Objective: The objective of the study was to evaluate the acute toxicity of the methanolic extract of the root-bark of F. zanthoxyloides, in mice. Methods: Methanolic extract of the root-bark of the plant was administered orally to mice at various dose levels to determine the acute toxic effects and the median lethal dose (LD50) in mice. Results: The LD50 of the methanolic extract was found to be 5.0 g/Kg body weight within 95 % confidence limits. The mice showed signs of cerebral irritation before dying. Histopathological examinations of the viscera showed congestion and focal necrosis of the liver and renal tubules. Conclusion: It was concluded that the extract of F. zanthoxyloides is safe, however the cerebral mechanism that lead to the death of the mice need to be investigated further.
A novel polymorphism in ABCB1 gene, CYP2B6*6 and sex predict single-dose efavirenz population pharmacokinetics in Ugandans.
(British Journal of Clinical Pharmacology, 2009) Mukonzo, Jackson K.; Röshammar, Daniel; Waako, Paul J; Andersson, Maria; Fukasawa, Takashi; Milani, Lili; Svensson, Jan Olof; Ogwal-Okeng, Jasper; Gustafsson, Lars L; Aklillu, Eleni
AIMS Efavirenz exhibits pharmacokinetic variability causing varied clinical response. The aim was to develop an integrated population pharmacokinetic/pharmacogenetic model and investigate the impact of genetic variations, sex, demographic and biochemical variables on single-dose efavirenz pharmacokinetics among Ugandan subjects, using NONMEM. METHODS Efavirenz plasma concentrations (n = 402) from 121 healthy subjects were quantified by high-performance liquid chromatography. Subjects were genotyped for 30 single nucleotide polymorphisms (SNPs), of which six were novel SNPs in CYP2B6, CYP3A5 and ABCB1. The efavirenz pharmacokinetics was described by a two-compartment model with zero- followed by first-order absorption. RESULTS Apparent oral clearance (95% confidence interval) was 4 l h l-1 (3.5, 4.5) in extensive metabolizers. In the final model, incorporating multiple covariates, statistical significance was found only for CYP2B6*6 and CYP2B6*11 on apparent oral clearance as well as ABCB1 (rs3842) on the relative bioavailability. Subjects homozygous for CYP2B6*6 (G516T, A785G) and *11 displayed 21 and 20% lower apparent oral clearance, respectively. Efavirenz relative bioavailability was 26% higher in subjects homozygous for ABCB1 (rs3842). The apparent peripheral volume of distribution was twofold higher in women compared with men. CONCLUSIONS The model identified the four factors CYP2B6*6, CYP2B6*11, a novel variant allele in ABCB1 (rs3842) and sex as major predictors of efavirenz plasma exposure in a healthy Ugandan population after single-dose administration. Use of mixed-effects modelling allowed the analysis and integration of multiple pharmacogenetic and demographic covariates in a pharmacokinetic population model.
Community effectiveness of malaria treatment in Uganda---a long way to Abuja targets
(Annals of tropical paediatrics : Taylor & Francis, 2013) Nsungwa-Sabiiti, Jesca; Tomson, Göran; Pariyo, George; Ogwal-Okeng, Jasper; Peterson, Stefan
ntroduction: At the Roll Back Malaria summit for African countries in Abuja, the heads of state committed to ensure that by the year 2005 at least 60% of those suffering from malaria would have access to effective treatment within 24 hours of onset of symptoms. Aim: The aim of the study was to assess community effectiveness of malaria treatment in children. Method: A community-based survey of 500 households was undertaken in western Uganda. Results: A total of 260 (52%) children were reported to have had fever within the previous 2 weeks: 87% received some kind of treatment, 44% were said to have been treated within 24 hours of onset of symptoms, 47% received appropriate anti-malarials, 25% received the correct dosage, and 24% took the drug for the recommended period of time; altogether, only 7% received all the treatment steps. Conclusion: With drug efficacies of 50–90%, we estimate a community effectiveness of 4–6%, which is far from the 2005 Abuja target. The greatest need for improvement in the Home Based Fever Management strategy is in reducing delay in treatment and improving dosage and duration of treatment.
Existing capacity to manage pharmaceuticals and related commodities in East Africa
(BioMed Central : Human Resources for Health, 2009) Waako, Paul J; Odoi-adome, Richard; Obua, Celestino.; Owino, Erisa; Tumwikirize, Winnie; Ogwal-Okeng, Jasper; Anokbonggo, Willy W; Matowe, Lloyd; Aupont, Onesky
Background: East African countries have in the recent past experienced a tremendous increase in the volume of antiretroviral drugs. Capacity to manage these medicines in the region remains limited. Makerere University, with technical assistance from the USAID supported Rational Pharmaceutical Management Plus (RPM Plus) Program of Management Sciences for Health (MSH) established a network of academic institutions to build capacity for pharmaceutical management in the East African region. The initiative includes institutions from Uganda, Tanzania, Kenya and Rwanda and aims to improve access to safe, effective and quality-assured medicines for the treatment of HIV/AIDS, TB and Malaria through spearheading in-country capacity. The initiative conducted a regional assessment to determine the existing capacity for the management of antiretroviral drugs and related commodities. Methods: Heads and implementing workers of fifty HIV/AIDS programs and institutions accredited to offer antiretroviral services in Uganda, Kenya, Tanzania and Rwanda were key informants in face-to-face interviews guided by structured questionnaires. The assessment explored categories of health workers involved in the management of ARVs, their knowledge and practices in selection, quantification, distribution and use of ARVs, nature of existing training programs, training preferences and resources for capacity building. Results: Inadequate human resource capacity including, inability to select, quantify and distribute ARVs and related commodities, and irrational prescribing and dispensing were some of the problems identified. A competence gap existed in all the four countries with a variety of healthcare professionals involved in the supply and distribution of ARVs. Training opportunities and resources for capacity development were limited particularly for workers in remote facilities. On-thejob training and short courses were the preferred modes of training. Conclusion: There is inadequate capacity for managing medicines and related commodities in East Africa. There is an urgent need for training in aspects of pharmaceutical management to different categories of health workers. Skills building activities that do not take healthcare workers from their places of work are preferred.
Effects of intervention measures on irrational antibiotics/antibacterial drug use in developing countries
(Health, 2014) Bbosa, Godfrey S; Wong, Geoff; Kyegombe, David B; Ogwal-Okeng, Jasper
is a global problem, especially in developing countries. This results in an increased emer-gence of resistance to most common bacteria, higher cost of treatment, prolonged hospitaliza-tion and adverse drug reactions. Interventions measures have been instituted to avert the problem but it still persists. A systematic review was conducted to determine the effect of dif-ferent interventions (education, managerial, di-agnostic tests, regulatory, economic and multi-faceted) on misuse of AB drugs in developing countries. A total of 722 articles were retrieved and 55 were reviewed. About 10.9% of the stu-dies were from Africa, 63.6% from Asia, 9.1% from Latin America, and 16.4% from Southeas-tern Europe. A total of 52.7% of the studies were from hospital settings, 5.5% from outpatient departments, 21.8% were from public health care facilities, 12.7% from private pharmacies/drug stores, and 7.3% from the communities. Educa-tion intervention had 27.3% studies, managerial had 20%, managerial/education had 3.6%, regu-latory had 9.1%, education/regulation had 9.1% and diagnostic had 3.6% studies. Multifaceted intervention had 27.3% studies, with 63% im-provement in appropriate AB doses prescribed, 2.6% mean number of AB encounter reduction, 23% AB prescription reduction, 18.3% generic AB prescription improvement, 32.1% reduction in AB use, 89% reduction in AB use in acute respiratory infection, 82% in surgery, 62.7% mean reduction in deliveries, 39% in STDs, 36.3% mean reduction in diarrhea, 14.6% mean reduc-tion AB use in malaria, and 6% - 11% in the cost of treating bacteria-resistant organisms. Also noted was 6.3% reductions in mean AB en-counters after 1 month of intervention, and then increased to 7.7% after 3 months thus lacking sustainability. Multifaceted interventions were ef- fective in reducing irrational AB drug use in the various health facilities and communities as well as reduction in the emergence of resistance to the commonest bacteria in the developing coun- tries though there was lack of sustainability or continuity of rational drug use over the time.
Effect of chronic alcohol consumption on the red blood cell count and RBC indices in the HIV infected patients on d4T/3TC/NVP drug regimen in Uganda
(International Journal of Basic & Clinical Pharmacology, 2013) Bbosa, Godfrey S; Kyegombe, David B; Anokbonggo, William W; Lubega, Aloysius; Mugisha, Apollo.; Ogwal-Okeng, Jasper
Alcohol consumption is common problem in Uganda. Among the types of alcohols consumed include beers, spirits, liqueurs, wines and traditional brew. These alcohols are easily accessible and consumed by many people including the HIV infected patients who are on the d4T/3TC/NVP regimen. The aim of this study was to determine the effect of chronic alcohol intake on the red blood cell count (RBC) and the RBC indices in the HIV-infected patients on d4T/3TC/NVP regimen. It was a case control study that used a repeated measures design model where serial measurements of the red blood cell count (RBC) and RBC indices were determined at 3 month interval for 9 months. A total of 41 HIV infected patients were recruited and grouped into two arms; the control group had 21 patients and the chronic alcohol group had 20 patients. The RBC and RBC indices of the whole blood were determined using automated hematological Coulter CBC-5 Hematology Analyzer system using standard procedures. The data was sorted into alcohol-use self reporting by WHO AUDIT tool and alcohol-use biomarkers groups. It was analysed using the SAS 2003 version 9.1 statistical package with the repeated measures fixed model. The means were compared using the student t-test. The mean MCV and MCH values in the chronic alcohol use group were higher than in the control group and there was a significant difference between the 2 groups (p<0.05) for both the WHO AUDIT tool group and chronic alcohol use biomarkers group. The mean RBC count, Hct, HGB and MCHC values in both the control and chronic alcohol use groups were within the normal reference ranges for both groups though the trend was lower in alcohol group. Chronic alcohol use affects the RBC and RBC indices in the HIV infected patients on d4T/3TC/NVP treatment regimen.
CYP2B6 genotype-based efavirenz dose recommendations during rifampicin-based antituberculosis cotreatment for a sub-Saharan Africa population
(Future Medicine Ltd: Pharmacogenomics, 2016) Mukonzo, Jackson K.; Bisaso, Ronald K.; Ogwal-Okeng, Jasper; Gustafsson, Lars L.; Owen, Joel S.; Aklillu, Eleni.
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.

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