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Item 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.Item 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, JasperThis 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).Item Access and use of medicines information sources by physicians in public hospitals in Uganda: a cross-sectional survey(African Health Sciences, 2008) Tumwikirize, Winifred A.; Ogwal-Okeng, Jasper; Vernby, Åsa; Anokbonggo, Willy W.; Gustafsson, Lars L.; Lundborg, Cecilia S.Background: Rational and cost-effective prescription of medicines requires up-to-date and readily accessible medicines information. There are several studies on availability and access to medicines information sources, but have been conducted only in high-income countries. Objective: To assess medicines information sources accessed by physicians in public hospitals in Uganda, and physicians’ opinion on establishment of a medicines information centre in the country. Methods: A cross-sectional survey including 369 physicians from six district, six regional and two university hospitals. Data was collected using a semi-structured self-administered questionnaire. Results Response rate was 91%. This included 31, 136 and 168 physicians from the district, regional and university hospitals, respectively. In the district hospitals the source of medicines information reported to be most available was colleagues (100%), while in the regional and university hospitals it was literature from pharmaceutical companies (98%) and hard copy of research publications (99%) respectively. The most frequently used source in the district and regional hospitals was National Standard Treatment Guideline (90% and 73% respectively), and colleagues in university hospitals (89%). Accessibility problems with reported available sources were commonest with research publications in medical journals, both hard copy and through the internet, MIMS, pharmacists and pharmacologists. Need for a medicines information centre was indicated by 80% of the respondents. Conclusion: Majority of the physicians in public hospitals in Uganda have limited access to unbiased drug information. Therefore, there is need to assess the feasibility of establishing a drug information centre, and then assess its use during a trial period. Key words: Medicines information, physicians, UgandaItem Field-adapted sampling of whole blood to determine the levels of amodiaquine and its metabolite in children with uncomplicated malaria treated with amodiaquine plus artesunate combination(Malaria Journal, 2009) Ntale, Muhammad.; Obua, celestino; Mukonzo, Jackson; Mahindi, Margarita; Gustafsson, Lars L; Beck, Olof; Ogwal-Okeng, JasperBackground: Artemisinin combination therapy (ACT) has been widely adopted as first-line treatment for uncomplicated falciparum malaria. In Uganda, amodiaquine plus artesunate (AQ+AS), is the alternative first-line regimen to Coartem® (artemether + lumefantrine) for the treatment of uncomplicated falciparum malaria. Currently, there are few field-adapted analytical techniques for monitoring amodiaquine utilization in patients. This study evaluates the field applicability of a new method to determine amodiaquine and its metabolite concentrations in whole blood dried on filter paper. Methods: Twelve patients aged between 1.5 to 8 years with uncomplicated malaria received three standard oral doses of AQ+AS. Filter paper blood samples were collected before drug intake and at six different time points over 28 days period. A new field-adapted sampling procedure and liquid chromatographic method was used for quantitative determination of amodiaquine and its metabolite in whole blood. Results: The sampling procedure was successively applied in the field. Amodiaquine could be quantified for at least three days and the metabolite up to 28 days. All parasites in all the 12 patients cleared within the first three days of treatment and no adverse drug effects were observed. Conclusion: The methodology is suitable for field studies. The possibility to determine the concentration of the active metabolite of amodiaquine up to 28 days suggested that the method is sensitive enough to monitor amodiaquine utilization in patients. Amodiaquine plus artesunate seems effective for treatment of falciparum malaria.Item 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, OneskyBackground: 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.Item 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, EleniAIMS 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.Item Phytochemicals and uses of Moringa oleifera leaves in Ugandan rural communities(Journal of Medicinal Plants Research, 2010) Kasolo, Josephine N; Bimenya, Gabriel S.; Ojok, Lonzy; Ochieng, Joseph; Ogwal-Okeng, JasperMoringa oleifera grown and used in many countries around the world is a multi-purpose tree with medicinal, nutritional and socio-economic values. In Senegal and Benin, M. oleifera leaves are dispensed as powder at health facilities to treat moderate malnutrition in children. It established the medicinal uses of M. oleifera leaves by local communities in Uganda and identified phytochemicals present in M. oleifera leaves extracts. It used quantitative and experimental methods that established the uses, and identified phytochemicals in M. oleifera leaves. Employed serial extractions, using ether, ethanol and water as solvents. The phytochemicals were qualitatively identified using standard chemicals and standard outcomes. Twenty-four medicinal uses of M. oleifera leaves were established. Phytochemicals present included: tannins, steroids and triterpenoids, flavonoids, saponins, anthraquinones, alkaloids and reducing sugars. The local communities in Uganda use M. oleifera leaves to treat common ailments. Presence of phytochemicals in the extracts, indicate possible preventive and curative property of M. oleifera leaves. There is need to standardize M. oleifera leaves use for nutrition and herbal medicine.Item 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.Item Adverse drug reactions in patients admitted on Internal Medicine wards in a district and Regional Hospital in Uganda(African Health Sciences, 2011) Tumwikirize, WA; Ogwal-Okeng, Jasper; Vernby, A; Anokbonggo, W; Gustafsson, L; Lundborg, sIntroduction: The burden of both community and hospital acquired adverse drug reactions (ADRs) are some of the important issues in pharmacotherapy. At the time of this study there was very scanty literature in this area from Africa. Objective: This study was done to determine the frequency and characteristics of ADRs in patients admitted on medical wards in public hospitals. Methods: This was a longitudinal observational study on 728 adult patients on medical wards in one regional and one district hospitals. Community and hospital acquired ADRs were assessed. Results: Thirty three patients (4.5%) were admitted with suspected ADR, and an ADR was the reason for hospitalization in 1.5%. Most ADRs were due to antiparasitic products, mainly quinine (61%). Community acquired ADRs prolonged hospital stay, 5.6 days vs 4.0 days (p-value < 0.001). During hospitalization ADRs occurred in 49.5% of the patients. Antiparasitic products, predominantly quinine, were the commonest drugs class associated with ADRs (85.9%). Hospital acquired ADRs did not affect hospital stay, 4.2 days vs 3.9 (p-value 0.129). Conclusion: ADRs are an important cause of morbidity in patients, both in the community and in hospitals, and the majority are associated with the commonly used drugsItem Phytochemicals and acute toxicity of Moringa oleifera roots in mice(Journal of Pharmacognosy and Phytotherapy, 2011) Kasolo, J. N.; Bimenya, G. S.; Ojok, L.; Ogwal-Okeng, JasperThe phytochemicals used by plants to protect themselves against predators in Moringa oleifera roots were qualitatively identified in the aqueous and ethanol extracts. Its acute toxicity in 24 h was evaluated in Swiss albino mice. M. oleifera, a native plant of the sub-Himalayan tracts of India, Pakistan, Bangladesh and Afghanistan is used in folk medicine. It is claimed to have nutritional, medicinal, socio-economic and industrial values. Many individuals and families consume the roots for their medicinal properties. Despite wide use the roots, the phytochemicals and toxicity profile are not well documented. This study set out to determine the phytochemicals and acute toxicity of M. oleifera roots in mice. The roots were harvested during dry season and air dried. Serial extractions using ether, ethanol and water were done. The harvested phytochemicals were qualitatively identified using standard chemicals procedures. The phytochemicals identified were: gallic tannins, catechol tennins, steroids and triterponoids, saponins, anthraquinones, alkaloids, and reducing sugars. Acute toxicity was determined by giving a single oral dose to Swiss albino mice and observed for 24 h. The LD50 was calculated using the probit tables. The LD50 of ethanol extract was 17.8 g/kg and that of aqueous extract was 15.9 g/kg. In conclusion, M. oleifera roots contain protective phytochemicals and are relatively non-toxic when given in a single dose.Item Use of a pilot drug information centre(African Health Sciences, 2011) Tumwikirize, A W; Ogwal-Okeng, Jasper; Vernby, A; Anokbonggo, W W; Gustafsson, L L; Lundborg, C SIntroduction: Provision of access to drug information by prescribers and other health care professionals is important in pharmacotherapy. At the time of this study there was very scanty literature in this area from Africa. Objective: To assess use of a pilot drug information centre (DIC) which was set up in a department of Pharmacology and Therapeutics in a university teaching hospital in Uganda. Methods: This was a situational analysis with a prospective study design. The pilot DIC was established and its use over an eleven-month period was assessed. The received queries were evaluated for source of the query, reason for the query and type of query. Results: During the 11 months 297 queries were received, 72.3% of which were from public hospitals. Most werefrom prescribing doctors (54.2%). Majority were on drug-drug interaction (41.2%), followed by therapy (23.2%). Out of 197 specific drug requests, 65.5% were on antiretroviral. Conclusion: We found that healthcare professionals were enthusiastically using the drug information centre. It is, therefore, necessary and feasible to establish a DIC in Uganda that will enable these professionals to readily access drug information.Item 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, CelestinoPurpose: 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.Item 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, OlwaMalaria 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.Item 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, MuhammadBackground: 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.Item Aflatoxins metabolism, effects on epigenetic mechanisms and their role in carcinogenesis(Health, 2013) Bbosa, Godfrey S.; Kitya, David; odda, John; Ogwal-Okeng, JasperChronic 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.Item 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, Stefanntroduction: 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.Item Review of the Biological and Health Effects of Aflatoxins on Body Organs and Body Systems(InTech, 2013) Bbosa, Godfrey S.; Kitya, David; Lubega, A.; Ogwal-Okeng, Jasper; Anokbonggo, William W.; Kyegombe, David B.Aflatoxins are a group of naturally occurring carcinogens that are known to contaminate different human and animal food stuffs. Aflatoxins are poisonous by-products from soil-borne fungus Aspergillus, which is responsible for the decomposition of plant materials [1-9]. The occurrence of aflatoxins foods and food products vary with geographic location, agricultural and agronomic practices. The susceptibility of food product to fungal attack occurs during pre-harvest, transportation, storage, and processing of the foods [1, 2, 4, 6, 9, 10]. The problem of aflatoxin contamination of the food products is a common problem in tropical and subtropical regions of the world especially in the developing countries such as the sub-Saharan countries with poor practices and where the environmental conditions of warm temperatures and humidity favors the growth fungi [1, 2, 4, 6, 9, 10]. The various food products contaminated with aflatoxins include cereals like maize, sorghum, pearl millet, rice and wheat; oilseeds such as groundnut, soybean, sunflower and cotton; spices like chillies, black pepper, coriander, turmeric and zinger; tree nuts such as almonds, pistachio, walnuts and coconut; and milk and milk products [11].Item 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, JasperAlcohol 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.Item Influence of efavirenz pharmacokinetics and pharmacogenetics on neuropsychological disorders in Ugandan HIV-positive patients with or without tuberculosis: a prospective cohort study(BMC Infectious Diseases, 2013) Mukonzo, Jackson K; Okwera, Alphonse; Nakasujja, Neoline; Luzze, Henry; Waako, Paul.; Ogwal-Okeng, Jasper; Gustafsson, Lars L; Aklillu, EleniBackground: 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.Item Chronic alcohol use affects therapeutic steady state plasma drug concentrations of stavudine, lamivudine and nevirapine in HIV-infected patients during 9 months follow up period: WHO AUDIT tool application(International Journal of Basic & Clinical Pharmacology, 2013) Bbosa, G.S; Kyegombe, D.B; Anokbonggo, W.W; Ntale, Muhammad; Musoke, D; Odda, John; Lubega, A; Ogwal-Okeng, JasperChronic alcohol consumption is a common problem among the HIV-infected patients on HAART. The study determined the effect of chronic alcohol use on steady state plasma drug concentrations of stavudine (d4T), lamivudine (3TC) and nevirapine (NVP) in HIV-infected patients during the 9 months follow up period. It also determined whether there were some patients with undetectable plasma drug concentrations in their plasma during the follow up. A case control using repeated measures design with serial measurements model, where plasma drug concentrations were measured at 3 month intervals was used. Chronic alcohol-use using WHO AUDIT tool was used to screen patients. A total of 41 patients (21 alcohol group and 20 control group) were followed up for 9 months with blood sampling done at 3 month intervals. The Shimadzu Class-VPTM HPLC Chromatography data system version 6.1 equipment with UV detector was used to measure the plasma drug concentrations. Data was analyzed using SAS 2003 version 9.1 statistical package with repeated measures fixed the model and means were compared using the student t-test. The mean steady state plasma concentration of both d4T and 3TC in chronic alcohol use group were lower than in the control group all throughout the 9 months period of follow-up. The mean steady state plasma drug concentrations of NVP were higher in the alcohol group at 0 and 3 months and lower in the 6 and 9 months as compared to the control group. The mean total plasma NVP concentration was higher in the chronic alcohol group as compared to the control group and the difference was statistically significant (p≤0.05). However some patients had undetectable plasma drug concentrations despite of having ≥ 95 % adherence rate. Chronic alcohol use by the HIV-infected patients lowers the steady state plasma drug concentrations of d4T, 3TC and NVP in patients.
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