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 AFB 1 are biotransformed to various metabolites especially the active AFB 1-exo-8,9-epoxide (AFBO). The AFB, AFBO and other metabolites interact with various biomolecules in the body including nucleic acids such as DNA and RNA and the various metabolic pathways such as protein synthesis, glycolytic pathway and electron transport 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 activates these nuclear receptors to produce the metabolizing enzymes. The AFB 1 is metabolized in the body by cytochrome P450 (CYP450) enzyme isoforms such as CYP1A2, CYP1A2, CYP3A4/ CYP3A5, and CYP3A7 in fetus, glutathione Stransferase, aflatoxin B 1-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 AFB 1-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, AFB 1-exo-8,9-epoxide and other metabolites also affect the epigenetic mechanisms including the DNA methylation, histone modifications, 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 epigenetic derepression and all these affect the gene expression, cellular differentiation and growth. AFB also through epigenetic mechanisms promotes tumorigenesis, angiogenesis, invasion and metastasis in hepatocellular carcinoma. However, the formation of the small amounts of AFB 1 from AFB 2 is suspected to cause the carcinogenicity of AFB 2 in humans and animals. Chronic aflatoxins exposure leads to formation of reactive AFBO metabolites in the body that could activate and deactivates the various epigenetic mechanisms leading to development of various cancers.

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.

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Background Malaria remains a major vector borne disease globally, with the majority of the casualties reported in Africa. Despite this fact, there is drastic reduction in malaria infection using Artemisinin combined therapies (ACTs). Malaria is characterized by significant inconsistency in different geographical locations due to different confounding factors. There is need to identify zone-specific malaria trends and interventions to completely eliminate the disease. Thus the study was aimed at assessing the 11-year trend of microscopically confirmed malaria cases in Kisii County, Kenya, so as to devise area-specific evidence-based interventions, informed decisions, and to track the effectiveness of malaria control programs. Methods This was a retrospective study carried out to determine 11-year malaria trend rates centered on the admission and laboratory records from health facilities located at four Sub-Counties in Kisii County, Kenya. Parasitological positivity rates of malaria were determined by comparing with the register records in health facilities which recorded confirmed malaria cases with the total number of monthly admissions over the entire year. Data was analyzed by using descriptive tools and chi-square test. Results There were 36,946 suspect cases, with 8449 (22.8%) confirmed malaria cases reported in this study. The overall malaria slide positivity rate over the last 11 years in the study area was 22.6%. The months of April and August showed the largest number of malaria cases (63%). The age group of ≥18 years contained the most positive confirmed cases, having a prevalence rate of 2953 (35.45%). Out of the confirmed malaria cases, 2379 (28.1%) were males and 6070 (71.9%) were females The highest malaria prevalence rate was recorded in 2014, with Marani Sub-County recording the highest positivity rate of 37.94%. Conclusion From the observed trends, malaria prevalence and transmission still remains stable in the study area. Thus more interventions need to be scaled up.

Introduction Drug resistance remains a major challenge in malaria treatment, especially after the emergence of resistance to artemisinin-based combined therapies. Plasmodium falciparum Kelch13 gene mutations are implicated in conferring artemisinin resistance. Thus, this study was aimed at determining the occurrence of Kelch13 ( K13 ) propeller resistance gene polymorphism mutations in Bushenyi district, Uganda. Methods Participants suspected to have malaria were recruited. P. falciparum was confirmed using antigen histidine-rich protein 2 (HRP2) (Pf) (Access Bio, Inc, USA) and microscopy. Malaria-positive patients were treated with artemeter-lumefantrine (AL). Blood was withdrawn from participants who tested positive for parasites after day 3 and kept in blood filter papers (ET31CHR; Whatman Limited, Kent, UK). DNA was extracted using chelex-suspension method. Nested polymerase chain reaction (PCR) was conducted and the second-round products sequenced using Sanger’s method. Sequenced products were analyzed using DNAsp 5.10.01 software and then blasted on to the NCBI for K13 -propeller gene sequence identity using the Basic Local Alignment Search Tool (BLAST). Results Out of 283 enrolled participants, 194 completed the follow-up schedule. A total of 134 (69%) had no parasites on day 3, while 60 (31%) had parasites on that day. Out of the 60 samples, 40 (62%) were positively amplified as P. falciparum , with polymorphisms in the K13 -propeller gene detected in 3 (7.5%) out of the 40 amplicons. Polymorphisms at codon 1929, 1788 and 1801 were detected separately in one sample each. Sequences have been deposited in NCBI with accession numbers PRJNA720348 and PRJNA720800. Conclusion Polymorphisms in the K13 -propeller gene previously reported to be associated with artemisinin resistance were not detected in the P. falciparum isolates from Bushenyi district, Uganda. More studies need to be conducted on the new mutations detected so as to understand their association, if any, with ACT resistance.

Introduction: Malaria remains the major vector borne disease in the world. Currently Kenya the ministry of health has scaled up interventions with chemotherapy and vector control standing out as a major strategy. Therefore, this study examined the influence of vector control and chemotherapy interventions on the treatment outcomes in Kisii County. Methods: Multi-stage random sampling was used for this study. The study was conducted from February 2021 to June 2021. Malaria-positive 275 participants were recruited into the study, treated with ACTs and followed for a period of 28 days at specified follow up days for parasite diagnosis. Occurrence of malaria clinical symptoms on the patients was also conducted. Molecular analysis was done by characterizing Merozoite proteins (MSP2) on the samples showing parasite recurrence. A Questionnaire was administered to determine the utilization of drugs for malaria treatment prior to this study and the usage of vector control after patient treatment with ACTs. Meanwhile, emphasis was laid on intervention strategies such as the use the usage of insecticide-treated nets (ITNs), Indoor residual spraying and chemotherapeutic practices as recommended by the World Health Organization (WHO). Results: Early treatment failure was reported among 27(12%) respondents, late clinical failures 20(8%), late parasitological failures 11(5%), and adequate clinical and parasitological outcomes 173(75%).Chemotherapeutic practices influencing treatment outcomes included; previous self-medication (OR=0.417; 95% CI: 0.153-1.385; p=0.035), ability of previously finishing doses (OR=0.328; 95% CI: 0.168-0.941; p=0.003,) and Frequency of previous antimalarial usage (OR=3.259; 95% CI: 1.054-4.721; p=0.004). While vector control interventions influencing treatment outcomes included; usage of indoor residual spraying (OR=0.408; 95% CI: 0.132-0.682; p=0.002), sleeping under the mosquito net (OR=0.218; 95% CI: 0.119-0.909; p=0.025,) and mosquito net treatment (OR=0.262; 95% CI: 0.092-0.823; p=0.003).With the molecular analysis detecting 10 samples with parasite recrudescence. Conclusions: Based on these findings, Antimalarial usage practices prior to current usage of ACTs and vector control after treatment remain important predictor factors for treatment outcomes.

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Chronic 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. [Int J Basic Clin Pharmacol 2013; 2(5.000): 507-516