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Edson Ireeta Munanura,1 Muhammad Ntale,2 John Wasswa,2 Bruhan Kaggwa1 1Department of Pharmacy, School of Health Sciences, College of Health Sciences, Makerere University, Kampala, Uganda; 2Department of Chemistry, School of Physical Sciences, College of Natural Sciences, Makerere University, Kampala, UgandaCorrespondence: Edson Ireeta Munanura, Tel +256740511609, Email eimunanura@gmail.comBackground: Human exposure to veterinary drugs like fluoroquinolones occurs due to the presence of their residues in foods from animal sources in varying concentrations. The existence of antibiotic residues in foodstuffs can pose great public health problems to consumers. This study aimed to assess enrofloxacin use patterns and assess residue levels of enrofloxacin/ciprofloxacin in breast muscle and liver tissues of broiler chickens sold for consumption in Kampala capital city.Methods: This was a cross-sectional study that involved both field survey and laboratory-based methods. The field study involved the use of qualitative and semi-quantitative data collection tools to interview 34 broiler farmers and 10 veterinary drugs vendors. For the determination of enrofloxacin/ciprofloxacin levels, 68 chicken breast and liver tissue samples were collected from main markets in Kampala over one month and analyzed using HPLC-UV.Results: Enrofloxacin was the most used antibiotic (100%) for the management of poultry diseases, majorly respiratory diseases (100%), salmonella infections (40%), and disease prevention (60%). Over 76% of the farmers knew the meat withdrawal time (WDT) for enrofloxacin, but none of them adhered to this. Over 70% of the farmers reported that the veterinary drugs vendors were not providing meat WDT information. Enrofloxacin/ciprofloxacin residues were identified in 35.3% (12/34) of the muscle and 38.2% (13/34) of the liver tissues analyzed. Of those muscle and liver tissue samples that tested positive, 25% (3/12) and 38.5% (5/13) respectively had drug concentrations higher than the recommended Maximum Residue Limits. The overall mean enrofloxacin/ciprofloxacin concentration in the chicken muscle and liver tissues was 83.6 (± 34.5) μg/kg and 171.5 (± 75.9) μg/kg.Conclusion: This observed presence of enrofloxacin/ciprofloxacin levels above safety requirements is attributable to inadequate medicines use information provided by veterinary drugs vendors to farmers and also to the non-compliance of some farmers to meat WDT due to the economic implications.Keywords: withdrawal time, maximum residue limits, enrofloxacin, food safety

The efficiency of recycled clays to bleach oils measured by decrease in absorbance of bleached oils was largest when recycled clays had been calcined at 450oC and leached in boiling mixture of 20% acid strength for 16 hours. The Langmuir constant a varied from 0.4x10-2 to 16 x10-2 and b increased from 4.7x10-2 to 95.38x10-2. The Freundlich constant n increased from 8x10-3 to 33x10-3 and k from 3.9x10-2 to 11.8 x10-2 as concentration of acid increased. The enthalpy of adsorption increased from -6.7x10-2 to 22.2x10-2 kJmol-1. [ABSTRACT FROM AUTHOR]

Background: Accumulation of chemicals including drugs in hair has been used in forensic investigations. Studies have reported isoniazid drug levels in the hair of TB patients., Objective: To review literature for evidence on isoniazid hair drug levels as a tool to monitor adherence, exposure, and TB treatment outcomes and the acceptability of using human hair for medical testing., Methods: We reviewed literature through Pubmed, Embase, Medline, google scholar, and google grey literature. The search terms focused on isoniazid/TB hair drug levels, adherence, treatment outcomes, and acceptability of using hair for medical testing. We kept refining our search terms at each step of our search., Results: The initial search yielded 186859 articles, which dropped to 88 after removing duplicates and irrelevant articles and eventually to 14 on further refining our search terms. On full review,2 out of 14 and 1 out of 14 articles touched the area of Isoniazid hair drug levels; adherence, exposure, TB treatment outcomes, and acceptability respectively. Further scrutiny showed that none of the articles had addressed our research question., Conclusion: Literature on Isoniazid hair drug levels among TB patients as a tool to monitor adherence, exposure, and TB treatment outcomes, and its acceptability is limited and more research is needed., Competing Interests: The authors declare to have no conflict of interest., (© 2023 Muzanyi G et al.)

Background: The current six months regimen for drug-susceptible tuberculosis (TB) is long, complex, and requires adherence monitoring. TB hair drug level assay is one innovative approach to monitor TB treatment adherence however, its acceptability in the context of African multi-cultural settings is not known., Objective: To determine the acceptability of hair harvest and testing as a TB therapeutic drug monitoring method., Methods: The study explored perceptions, and lived experiences among TB patients with regard to using hair harvest and testing as a method of tuberculosis therapeutic drug monitoring in the context of their cultural beliefs, and faith. We used a descriptive phenomenological approach., Results: Four main themes emerged namely: participants' perceptions about the cultural meaning of their body parts; perceptions about hair having any medical value or meaning; perceptions about hospitals starting to use hair harvest and testing for routine hospital TB treatment adherence monitoring; and perceived advantages and disadvantages of using hair for treatment adherence monitoring. Overall, we found that using hair to monitor adherence was acceptable to TB patients provided the hair was harvested and tested by a medical worker., Conclusion: Hair harvest for medical testing is acceptable to TB patients on the condition that it is conducted by a medical worker., (© 2023 Muzanyi G et al.)

Background: Antiretroviral hair drug levels are currently being used to monitor adherence to HIV treatment. There is currently a dearth of literature on the preferred technique(s) of hair harvest for medical testing in the context of African multicultural settings., Objective: To explore the preferred techniques(s) of hair harvest for medical testing among TB patients., Methods: We used a descriptive phenomenological approach to conduct interviews for 15 TB patients from the 06 th through the 24 th of June 2022. Data was organized by N-VIVO version 10 and analysed step by step using a thematic analytical approach., Results: Participants aged <30 years were more knowledgeable, positively perceived, and experienced about the salon-based hair cutting technique compared to those aged≥30 years old. Participants aged ≥30 had experience, flexibility to use, and were knowledgeable in all three techniques, Overall, for all age categories (<30,30-40 and >40 years), majority of the respondents were knowledgeable, flexible and experienced in using all the three techniques., Conclusion: The majority of TB patients were knowledgeable, experienced and flexible about the hair cutting techniques however, efforts are needed to educate the youth that hair for medical testing can be cut by any of the three techniques without changing their cosmetic look., Competing Interests: The authors declare t have no conflict of interest., (© 2023 Muzanyi G et al.)

The physical and chemical structure of activated carbon (AC) varies with the carbonization temperature, activation process and time. The texture and toughness of the starting raw material also determine the morphology of AC produced. The Brunauer-Emmet-Teller surface area (S BET ) is small for AC produced at low temperatures but increases from 500 to 700 °C, and generally drops in activated carbons synthesized > 700 °C. Mild chemical activators and low activator concentrations tend to generate AC with high S BET compared to strong and concentrated oxidizing chemicals, acids and bases. Activated carbon from soft starting materials such as cereals and mushrooms have larger S BET approximately twice that of tough materials such as stem berks, shells and bones. The residual functional groups observed in AC vary widely with the starting material and tend to reduce under extreme carbonization temperatures and the use of highly concentrated chemical activators. Further, the adsorption capacity of AC shows dependency on the size of the adsorbate where large organic molecules such as methylene blue are highly adsorbed compared to relatively small adsorbates such as phenol and metal ions. Adsorption also varies with adsorbate concentration, temperature and other matrix parameters., (© 2023. The Author(s).)

Phosphate is considered the main cause of eutrophication and has received considerable attention recently. Several methods have been used for removal of phosphates in water and these include biological treatment, membrane filtration processes, chemical precipitation, and adsorption. Adsorption technology is highly effective in the removal of phosphate from wastewater even at low phosphate concentrations. Nanomaterials/nanoparticles, carbon-based materials (activated carbon and biochar), and their composites have been widely employed for the adsorptive removal and recovery of phosphate from wastewater due to their exceptional properties such as high surface area and high phosphate adsorption properties. This article is a review of the recently reported literature in the field of nanotechnology and activated carbon for the adsorption of phosphate from wastewater. Highlights of the adsorption mechanisms, adsorption behaviour, experimental parameters, effects of co-existing ions, and adsorbent modifications are also discussed.

The study carried out a primary validation of Charm II tests for the detection of antimicrobial residues in aquaculture fish. The validation was performed according to European Commission Decision 2002/657/ EC and the parameters determined included: detection capability, repeatability, reproducibility, specificity and robustness for the detection of antimicrobial residues in fish. Fish materials from different species including cat fish, trout, salmon, sea bass, tilapia, lingue and pangasius, were spiked with varying concentrations of selected antimicrobials including sulfonamides, β-lactams, macrolides, tetracyclines and aminoglycosides to determine the detection capabilities and other validation parameters of the Charm II tests. Results of the validation showed that the detection capabilities for the tetracyclines ranged from 25 to 100 µg/kg, while the sulfonamides and aminoglycosides were detected at 25 µg/kg for all species under study. The detection capabilities for the beta-lactams ranged from 25 to 300 µg/kg; and was 100 µg/kg for the tested macrolides. Results of the study showed that there was no significant difference between counts for samples read immediately after addition of the scintillation liquid and those read 14 h after addition of the scintillation liquid, provided that there was good vortexing before analysis. There was also no significant difference between counts for the same samples analyzed in different runs under repeatability and reproducibility conditions at the same spiking concentrations for the different fish species analyzed. The relative standard deviation for both repeatability and reproducibility ranged from 1.2 to 15.1%. The Charm II tests were found to be 100% group specific, as none of the antimicrobials kits, gave false positive results when testing non-target antimicrobial drugs. Results of this study demonstrate the suitability of the Charm II technique as a rapid screening tool for detection of antimicrobial residues in a variety of fish species at maximum residue limits (MRL) established in the EU guidelines, with the exception of tilmicosin which was detected at 2 MRL. The results also prove the robustness, specificity, reliability and precision of the Charm II assay in the detection of various antimicrobial residuals in fish and its applicability for the rapid evaluation of the quality of aquaculture fish for safety and trade purposes., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

This study has been done with the objective of knowing more about the Anopheles evolutions situation at Lwiro-Katana from 1967 up to 2014. On seven species identified in this region, only four were permanent in nine investigations done. The geometric average calculated shows the evolution of 3.152 for Anopheles funestus, 2.867 for An. gambiae, 2.663 for An. demeilloni and 2.441 for An. marshallii. These species share almost the same ecological conditions for their larval development found in different kinds of water. These conditions were created by the anthropisation of the region followed by some activities. The increasing process attests that An. funestus, An. gambiae and An. demeilloni have an increasing tendency while An. marshallii has a decreasing tendency and is likely to approach the 0 level. An. coustani and An. christyi miss the stability development due to the environmental pertubations since 1980 in this environment. An. kingi wasn't identified after 1980. All of these species of anopheles share the same ecological niche and present a scientific interest. The knowledge of their evolution in this area is really very important because it helps to have better vector control. Also three of those mosquitos (An. gambiae, An. funestus and An. marshallii) are the greatest responsible of the killing paludism South of the Sahara.

Background: Sulphadoxine-pyrimethamine (SP) is widely used as an intermittent preventive treatment for malaria in pregnancy (IPTp). However, pharmacokinetic studies in pregnancy show variable and often contradictory findings. We describe population and trimester-specific differences in SP pharmacokinetics among Ugandan women., Methods: SP (three tablets) were administered to 34 nonpregnant and 87 pregnant women in the second trimester. Seventy-eight pregnant women were redosed in the third trimester. Blood was collected over time points ranging from 0.5 h to 42 days postdose. Data on the variables age, body weight, height, parity, gestational age, and serum creatinine, alanine transaminase and albumin levels were collected at baseline. Plasma drug assays were performed using high-performance liquid chromatography with ultraviolet detection. Population pharmacokinetic analysis was done using NONMEM software., Results: A two-compartment model with first-order absorption and a lag time best described both the sulphadoxine and pyrimethamine data. Between trimesters, statistically significant differences in central volumes of distribution (V(2)) were observed for both drugs, while differences in the distribution half-life and the terminal elimination half-life were observed for pyrimethamine and sulphadoxine, respectively. Significant covariate relationships were identified on clearance (pregnancy status and serum albumin level) and V(2) (gestational age) for sulphadoxine. For pyrimethamine, clearance (pregnancy status and age) and V(2) (gestational age and body weight) were significant. Considering a 25 % threshold for clinical relevance, only differences in clearance of both drugs between pregnant and nonpregnant women were significant., Conclusion: While clinically relevant differences in SP disposition between trimesters were not seen, increased clearance with pregnancy and the increasing volume of distribution in the central compartment with gestational age lend support to the revised World Health Organization guidelines advocating more frequent dosing of SP for IPTp.

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

Co-administration of artemether-lumefantrine with milk is recommended to improve lumefantrine (L) absorption but milk may not be available in resource-limited settings. This study explored the effects of cheap local food in Uganda on oral bioavailability of lumefantrine relative to milk. In an open-label, four-period crossover study, 13 healthy adult volunteers were randomized to receive a single oral dose of artemether-lumefantrine (80 mg artemether/480 mg lumefantrine) with water, milk, maize porridge or maize porridge with oil on separate occasions. Plasma lumefantrine was assayed using high-performance liquid chromatography with ultraviolet detection. Pharmacokinetic exposure parameters were determined by non-compartmental methods using WinNonlin. Peak concentrations (Cmax ) and area under concentration-time curve restricted to 48 hr after single dosing (AUC(0-48) ) were selected for relative bioavailability evaluations using confidence interval approach for average bioequivalence. Lumefantrine exposure was comparable in milk and maize porridge plus oil study groups. When artemether-lumefantrine was administered with maize porridge plus oil, average bioequivalence ranges (means ratios 90% CI, 0.84-1.88 and 0.85-1.69 for Cmax and AUC(0-48) , respectively) were within and exceeded acceptance ranges relative to milk (90% CI, 0.80-1.25). Both fasted and maize porridge groups demonstrated similarly much lower ranges of lumefantrine exposures (bioinequivalence) relative to milk. If milk is not available, it is thus possible to recommend fortification of carbohydrate-rich food with little fat (maize porridge plus vegetable oil) to achieve similarly optimal absorption of lumefantrine after artemether-lumefantrine administration., (© 2013 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.)

Background: Malaria in pregnancy is a major health problem that can cause maternal anaemia, stillbirth, spontaneous abortion, low birth weight and intra-uterine stunting. The WHO recommends use of sulphadoxine-pyrimethamine (SP) for intermittent preventive treatment of malaria during pregnancy (IPTp) in endemic areas. Towards monitoring and assessing IPTp coverage in the population, the Roll Back Malaria Partnership recommends the use of self-reported data. The aim of this study was to assess the validity of self-reported IPTp by testing for sulphadoxine in maternal blood at delivery., Methods: Two hundred and four pregnant women were consented and enrolled in a cross-sectional study in Mulago National Referral Hospital in Kampala Uganda. - Participants who reported a history of taking sulpha-containing drugs like co-trimoxazole , those who were not sure of dates relating to last menstrual period or who took IPTp within the first 20 weeks of gestation were excluded from the study. Data on demographic characteristics, obstetric history, and delivery outcome were collected. At birth, maternal venous blood was taken off aseptically and used to make thick blood smears for malaria parasites and plasma for determining sulphadoxine using high performance liquid chromatography (HPLC)., Results: Of 120 participants who self reported to have used IPTp, 35 (29.2%) tested positive for sulphadoxine by HPLC, while 63 (75%) of 84 patients who reported not having used IPTp tested negative for sulphadoxine. Participants possessing post-primary education were more likely to have reported using IPTp. The low agreement (kappa coefficient = 0.037) between self-report and actual presence of the drug in the blood casts doubt on the validity of self-reported data in estimating IPTp coverage., Conclusions: The results of this study question the accuracy of self-reported data in estimating IPTp coverage in the population. More studies on validity of self reported data are recommended. Since the validity of IPTp self reports is vital for guiding policy on malaria control in pregnancy, ways should be sought to improve accuracy of the information from such reports.

Introduction. Adherence to antiretroviral therapy (ART) in low-income countries is mainly assessed by self-reported adherence (S-RA) without drug level determination. Nonadherence is an important factor in the emergence of resistance to ART, presenting a need for drug level determination. Objective. We set out to establish the relationship between plasma stavudine levels and S-RA and validate S-RA against the actual plasma drug concentrations. Methods. A cross-sectional investigation involving 234 patients in Uganda. Stavudine plasma levels were determined using high-performance liquid chromatography. We compared categories of plasma levels of stavudine with S-RA using multivariable logistic regression models. Results. Overall, 194/234 patients had S-RA ≥ 95% (good adherence) and 166/234 had stavudine plasma concentrations ≥ 36 nmol/L (therapeuticconcentration). Patients with good S-RA were eight times more likely to have stavudine levels within therapeutic concentration (Adjusted Odds Ratio: 7.7, 95% Confidence Interval: 3.5-7.0). However, of the 194 patients with good S-RA, 21.7% had below therapeutic concentrations. S-RA had high sensitivity for adherence (91.6%), but limited specificity for intrinsic poor adherence (38.2%). Conclusions. S-RA is a good tool for assessing adherence, but has low specificity in detecting nonadherence, which has implications for emergence of resistance.

Background: 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(R) (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.

What Is Already Known About This Subject: * Both chloroquine (CQ) and sulfadoxine/ pyrimethamine (SDx/PYR) remain important drugs in the control of malaria. * The available data on CQ, SDx and PYR are summary pharmacokinetic parameters based on classical/traditional methods, mostly in adults. * No study has described the population pharmacokinetics of a fixed-dose CQ + SDx/PYR combination in children with falciparum malaria., What This Study Adds: * This study presents population pharmacokinetic data on CQ and SDx in children with uncomplicated falciparum malaria. * The study demonstrates that in age-based fixed-dose regimens with CQ and SDx, drug exposures and outcomes may be correctly predicted, although correlation with body weight is poor. * The study proposes dose modification to improve response with the CQ + SDx/PYR combination., Aims: To describe the pharmacokinetics of chloroquine (CQ) and sulfadoxine (SDx), and to identify predictors of treatment response in children with malaria given the CQ + SDx and pyrimethamine (PYR) combination., Methods: Eighty-six Ugandan children with uncomplicated falciparum malaria, 6 months to 5 years old, were randomly treated with prepacked fixed-dose CQ + SDx/PYR. The youngest children (<24 months) received half strength and the older (>24 months) full strength treatment. The reported day 14 failure rates were 48% and 18%, respectively. Capillary blood (100 microl) applied on to filter paper was collected on eight occasions during 28 days of follow up. Concentrations of CQ and SDx were determined. A population approach was used for the pharmacokinetic analysis., Results: A two-compartment model adequately described the data for both CQ and SDx. For CQ, the typical apparent clearance (CL/F) and volume of distribution (V(C)/F) values were estimated to be 2.84 l h(-1) and 230 l. The typical CL/F for SDx was 0.023 l h(-1), while the factor relating its V(C)/F to normalized body weight was 1.6 l kg(-1). Post hoc parameter estimates for both drugs showed lower maximum concentrations (C(max)) and concentration-time curve areas (AUC(0,336 h)) in younger children. The AUC(0,336 h) for SDx and CQ were independently significant factors for prediction of cure. Simulations suggest that giving the higher dose to the youngest children would result in higher CQ and SDx concentrations and improved outcome., Conclusions: The study results suggest that full-strength combination to all children would improve the cure rate.

Background: A pre-packaged fixed-dose formulation of chloroquine (CQ) and sulfadoxine/pyrimethamine (S/P) combination (Homapak) is widely used for the treatment of falciparum malaria in Ugandan children. It is however a product whose pharmacokinetics and interactions have not been studied., Objectives: To explore possible pharmacokinetic interactions between CQ and S/P during co-administration, and to determine their bioavailability in the locally made Homapak compared to the Good Manufacturing Practice (GMP) made formulations., Methods: Thirty-two adult healthy volunteers were randomized into four groups and given single oral doses of fixed-dose CQ+S/P combination (Homapak), or GMP formulations of S/P (Fansidar), CQ (Pharco), or their combination. Plasma samples were followed for 21 days, analysed by HPLC-UV methods, with pharmacokinetic modeling using the WinNonlin software., Results: Sulfadoxine in Homapak was more rapidly absorbed (ka = 0.55 h(-1)) than in Fansidar + CQ (ka = 0.27 h(-1), p=0.004), but not more than S in Fansidar alone group (ka = 0.32 h(-1), p=0.03). No significant differences were observed in the other pharmacokinetic parameters of S, P and CQ when given together or separately. The relative bioavailability of CQ and S in Homapak showed bioequivalence to reference formulations., Conclusions: There were no pharmacokinetic interactions between CQ, S and P when the compounds were given together, however, more investigations would be needed to explore this further. Compared with GMP made drugs, both S and CQ are bioequivalent in Homapak, the Ugandan made fixed-dose formulation. Furthermore, the absorption of S was more rapid which could be advantageous in malaria treatment.