Contribution of Sub-Saharan African medicinal plants to cancer research: Scientific basis 2013-2023.

Cancer incidence and mortality rates are increasing worldwide. Cancer treatment remains a real challenge for African countries, especially in sub-Saharan Africa where funding and resources are very limited. High costs, side effects and drug resistance associated with cancer treatment have encouraged scientists to invest in research into new herbal cancer drugs. In order to identify potential anticancer plants for drug development, this review aims to collect and summarize anticancer activities (in vitro/in vivo) and molecular mechanisms of sub-Saharan African medicinal plant extracts against cancer cell lines. Scientific databases such as ScienceDirect, Google Scholar and PubMed were used to search for research articles published from January 2013 to May 2023 on anticancer medicinal plants in sub-Saharan Africa. The data were analyzed to highlight the cytotoxicity and molecular mechanisms of action of these listed plants. A total of 85 research papers covering 204 medicinal plant species were selected for this review. These plants come from 57 families, the most dominant being the plants of the family Amaryllidaceae (16), Fabaceae (14), Annonaceae (10), Asteraceae (10). Plant extracts exert their anticancer activity mainly by inducing apoptosis and stopping the cell cycle of cancer cells. Several plant extracts from sub-Saharan Africa therefore have strong potential for the search for original anticancer phytochemicals. Chemoproteomics, multi-omics, genetic editing technology (CRISPR/Cas9), combined therapies and artificial intelligence tools are cutting edge emerging technologies that facilitate the discovery and structural understanding of anticancer molecules of medicinal plants, reveal their direct targets, explore their therapeutic uses and molecular bases.

Exploring antibiotic-induced persister formation and bacterial persistence genes in clinical isolates from Burkina Faso.

BACKGROUND: In addition to antibiotic resistance, persistence is another cause of treatment failure in bacterial infections, representing a significant public health concern. Due to a lack of adequate data on clinical isolates, this study was initiated to investigate persistence in clinical isolates in Burkina Faso. METHODS: Eighty (80) clinical isolates, including 32 Pseudomonas aeruginosa, 41 Staphylococcus aureus, and 7 Salmonella sp. obtained from clinical laboratories in Burkina Faso, were analyzed to assess their susceptibility to ciprofloxacin and gentamicin, as well as to determine the presence of persistence genes. The effects of ciprofloxacin and gentamicin on persister formation were evaluated by conducting colony counts at 1, 3, 5, 7, and 20 h after exposing the bacteria to high concentrations of these antibiotics. RESULTS: Results showed high sensitivity to both antibiotics (72.5% for ciprofloxacin and 82.5% for gentamicin). Persister formation occurred in Staphylococcus aureus with gentamicin and in Salmonella sp. with ciprofloxacin, while Pseudomonas aeruginosa did not form persisters. The mazF gene was found in 28.13% of P. aeruginosa and 2.44% of S. aureus isolates, and the hipA gene in 28.57% of Salmonella sp. None of the relE1 or relE2 genes were detected. CONCLUSIONS: The study revealed high sensitivity in clinical bacterial isolates to ciprofloxacin and gentamicin. Staphylococcus aureus and Salmonella sp. showed persister formation under antibiotic stress, with low frequencies of the studied persistence genes. These findings enhance understanding of clinical bacterial behavior and inform strategies against antibiotic-resistant infections.

Rotavirus vaccines in Africa and Norovirus genetic diversity in children aged 0 to 5 years old: a systematic review and meta-analysis : Rotavirus vaccines in Africa and Norovirus genetic diversity.

Noroviruses are the second leading cause of death in children under the age of 5 years old. They are responsible for 200 million cases of diarrhoea and 50,000 deaths in children through the word, mainly in low-income countries. The objective of this review was to assess how the prevalence and genetic diversity of noroviruses have been affected by the introduction of rotavirus vaccines in Africa. PubMed, Web of Science and Science Direct databases were searched for articles. All included studies were conducted in Africa in children aged 0 to 5 years old with gastroenteritis. STATA version 16.0 software was used to perform the meta-analysis. The method of Dersimonian and Laird, based on the random effects model, was used for the statistical analyses in order to estimate the pooled prevalence's at a 95% confidence interval (CI). Heterogeneity was assessed by Cochran's Q test using the I2 index. The funnel plot was used to assess study publication bias. A total of 521 studies were retrieved from the databases, and 19 were included in the meta-analysis. The pooled norovirus prevalence's for pre- and post-vaccination rotavirus studies were 15% (95 CI, 15-18) and 13% (95 CI, 09-17) respectively. GII was the predominant genogroup, with prevalence of 87.64% and 91.20% respectively for the pre- and post-vaccination studies. GII.4 was the most frequently detected genotype, with rates of 66.84% and 51.24% respectively for the pre- and post-vaccination studies. This meta-analysis indicates that rotavirus vaccination has not resulted in a decrease in norovirus infections in Africa.

Predominance of DENV-3 among patients in Ouagadougou, Burkina Faso.

BACKGROUND OBJECTIVES: Dengue is an emerging vector-borne viral disease in tropical and subtropical areas such as Burkina Faso that experienced dengue outbreak in, 2013, 2016, 2017 and more recently in 2023. This study aimed to determine the seroprevalence and dengue serotype in suspected patients in Ouagadougou, Burkina Faso. METHODS: The study was conducted during October and November 2023 and included suspected febrile patients seen at HOSCO and CERBA. Plasma or serum samples were used for the detection of non-structural proteins (NS1) and IgM and IgG antibodies against the dengue virus using SD Bioline Dengue Duo rapid detection kit. Viral RNA was extracted using the QIAamp Viral RNA Mini Kit and dengue serotypes were determined by real-time RT-PCR using the Dengue Real-TM Genotype kit. RESULTS: The study population consisted of 896 patients, including 397 (44.3%) men and 499 (55.7%) women. Dengue seroprevalence was 16.5% (148/896) with 14.1% (126/896) of patients positive for the NS1 antigen, 1.3% (12/896) positive for IgM, and 2.7% (24/896) positive for IgG. Serotyping among 40 out of 45 positive patients revealed 77.5% (31/40) DENV-3, 17.5% (7/40) DENV-1, and 5.0% (2/40) DENV-2. INTERPRETATION CONCLUSION: The present study report a high seroprevalence of dengue virus infection among patients during the months considered as the peak of infection in Burkina Faso. The results revealed a predominance of DENV-3. Continuous surveillance of dengue virus serotypes circulating in Burkina Faso is crucial.

Prevalence and patterns of chromosomal abnormalities in patients suspected of genetic disorders: insights from a study in Ouagadougou, Burkina Faso.

BACKGROUND: Chromosomal abnormalities contribute significantly to human morbidity and mortality, leading to various pathologies. This study aimed to assess the prevalence of chromosomal abnormalities among patients suspected of genetic disorders in Ouagadougou, Burkina Faso. METHODS AND RESULTS: A descriptive cross-sectional study was conducted from January 1, 2018, to July 16, 2021, involving patients from different university hospitals in Ouagadougou. Blood samples were collected at Hôpital Saint Camille de Ouagadougou (HOSCO) and sent to the Cerba laboratory in France for cytogenetic analysis. A total of 61 cases with suspected genetic disorders were referred for cytogenetic examination. The average age of the patients was 26.81 years ± 18.92, ranging from 1 month to 68 years. Among the cases, 37 (60.65%) exhibited chromosomal abnormalities. Structural abnormalities were the most prevalent (78.38%), while number anomalies accounted for 21.62% of the cases. Chronic myeloid leukemia was detected in 59.45% of cases, followed by free and homogeneous trisomy 21 (18.91%) and sexual inversion (8.10%). Additionally, one case each of Turner syndrome and Klinefelter syndrome were identified. CONCLUSION: This this study revealed a high frequency of chromosomal abnormalities, with a predominance of structural abnormalities, among patients suspected of genetic disorders in Ouagadougou. The findings emphasize the significance of genetic evaluation and counseling services in the region, particularly for autosomal abnormalities.

Association of DRB1*11 and DRB1*12 alleles of the HLA system with the evolution of the Hepatitis B virus infection in Burkina Faso.

BACKGROUND: Hepatitis B Virus (HBV) infection affect all social strata of humanity and in the absence of any management, this infection has a different outcome from one infected person to another. This suggests that there are specific individual factors that influence the outcome of the pathology. Sex, immunogenetics and age of contraction of the virus have been cited as factors that influence the evolution of the pathology. In this study, we looked at two alleles of the Human Leucocyte Antigen (HLA) system to measure their possible involvement in the evolution of HBV infection. METHOD AND RESULTS: We conducted a cohort study involving 144 individuals spread over 04 distinct stages of infection and then compared allelic frequencies in these populations. A multiplex PCR was conducted and the data obtained was analyzed using R and SPSS software. Our study revealed a predominance of HLA-DRB1*12 in our study population without, however, showing a significant difference between HLA-DRB1*11 and HLA-DRB1*12. The HLA-DRB1*12 proportion was significantly higher in chronic hepatitis B (CHB) and resolved hepatitis B (RHB) compared to cirrhosis and hepatocellular carcinoma (HCC) (p-value = 0,002). Carrying HLA-DRB1*12 has been associated with a low risk of complication of infection (CHB → cirrhosis; OR 0,33 p-value 0,017; RHB → HCC OR 0,13; p-value = 0,00,045) whereas the presence of HLA-DRB1*11 in the absence of HLA-DRB1*12 increased the risk of developing severe liver disease. However, a strong interaction of these alleles with the environment could modulate the infection. CONCLUSION: Our study shown that HLA-DRB1*12 is the most frequent and it's carriage may be protective in the development of infection.

Chemical Composition of Essential Oil of Cymbopogon schoenanthus (L.) Spreng from Burkina Faso, and Effects against Prostate and Cervical Cancer Cell Lines.

The aim of this research was to evaluate the essential oil of Cymbopogon schoenanthus (L.) Spreng. (C. schoenanthus) from Burkina Faso in terms of cytotoxic activity against LNCaP cells, derived from prostate cancer, and HeLa cells, derived from cervical cancer. Antioxidant activities were evaluated in vitro. Essential oil (EO) was extracted by hydrodistillation and analyzed by GC/FID and GC/MS. Thirty-seven compounds were identified, the major compounds being piperitone (49.9%), δ-2-carene (24.02%), elemol (5.79%) and limonene (4.31%). EO exhibited a poor antioxidant activity, as shown by the inhibition of DPPH radicals (IC50 = 1730 ± 80 µg/mL) and ABTS+. (IC50 = 2890 ± 26.9 µg/mL). Conversely, EO decreased the proliferation of LNCaP and HeLa cells with respective IC50 values of 135.53 ± 5.27 µg/mL and 146.17 ± 11 µg/mL. EO also prevented LNCaP cell migration and led to the arrest of their cell cycle in the G2/M phase. Altogether, this work points out for the first time that EO of C. schoenanthus from Burkina Faso could be an effective natural anticancer agent.

BRCA1, BRCA2, TP53, PIK3CA, PTEN and AKT1 genes mutations in Burkina Faso breast cancer patients: prevalence, spectrum and novel variant.

BRCA1 and BRCA2 are the two most commonly mutated tumor suppressor genes associated with hereditary breast cancer (BC). Also, mutations in TP53, PIK3CA, PTEN and AKT1 were observed at a high frequency in BC with their mutation spectrum exhibiting a subgroup particularity with enormous clinical significance in the prevention, classification and treatment of cancers. Unfortunately, the mutation spectrum of these genes is still unknown in most Sub-Saharan African population. Therefore, using samples from 133 unselected BC patients, we aimed to assess the contribution of these mutations by direct Sanger sequencing. The analysis revealed pathogenic germline variants on BRCA1 exon 11 (c.3331C > T, 0.75%) and BRCA2 exon 11 (c.5635G > T, c.6211delA; 1.5%). Five other pathogenic variants were identified in 61 of the 133 subjects (45.86%), with 39.09% for PIK3CA, 12.78% for TP53. Interestingly, a variant in PIK3CA found in high frequency in our population was different from the one usually found in other populations (c.1634A > C, 38.34%), and four patients carried mutations linked to Cowen Syndrome 5 c.[1634A > C;1658_1659delGTinsC]. A novel variant (c.312G > T) was found in TP53 gene at 12.78%. Overall, mutation carriers were found more in Her2 negative and in patients that underwent surgery and chemotherapy. No pathogenic variant was found in PTEN and AKT1. Our population displayed a high frequency of PIK3CA mutations with an unusual distribution and spectrum as well as a relatively low prevalence of BRCA mutations. Our results provided novel data on an unstudied population and may help in prevention, and the establishment of suitable therapeutic approaches for our population.

KIR2DL5B and HLA DRB1*12 alleles seems to be associated with protection against HIV-1 in serodiscordant couples in Burkina Faso.

The human immunodeficiency virus (HIV) belongs to the Retroviridae family and remains a public health problem in sub-Saharan Africa. Recent reports from WHO have shown that 33 million people died from HIV infections. HIV is one of the most serious fatal human diseases of the 20th and 21st centuries. However, variations in genetic and immunological factors are associated with protection against HIV infection in uninfected people exposed to HIV. This is the case with naturals killers which play an important role in the progression or regression of HIV infection. The objective of this study is to characterize certain HLA (human leukocyte antigen) class II genes and KIR genes in HIV-1 serodiscordant couples in Burkina Faso. This study was carried out at Burkina Faso among nineteen (19) HIV-1 serodiscordant couples. Classical multiplex PCR (SSP-PCR) was used to characterize the presence or absence of the KIR genes and certain class II HLAs (DRB1*11 and DRB1*12). The characterization of the KIR and HLA genes DRB1*11, DRB1*12 in this study demonstrated that the inhibitor KIR2DL5B, would confer protection against HIV-1 infection in seronegative partners (odd ratio [OR] = 0.13 [0.02-0.72] and p = 0.029), and the HLA DRB1*12 allele was associated with protection against HIV-1 infection in seronegative partners (OR = 0.16 [0.03-0.77] and p = 0.038). AA and Bx haplotypes were not found to be associated with HIV-1 infection in serodiscordant couples. This study confirms the involvement of the KIR genes in viral pathologies such as HIV-1 infection. Future larger-scale studies may provide a better understanding of the molecular mechanism by which the KIR haplotype and combination of KIR/HLA are associated with protection against HIV infection.

Performance of Molecular Tests in the Diagnosis of Syphilis From 2009 to 2019: A Systematic Review and Meta-Analysis.

BACKGROUND: Syphilis continues to be a public health problem, and its diagnosis still has limitations. Molecular diagnosis provides an alternative for rapid and effective management. The objective is to determine the accuracy of tests in the molecular diagnosis of syphilis. METHODS: We searched PubMed and Web of Sciences for articles related to molecular detection of syphilis from January 1, 2009, to December 31, 2019. The bivariate Reitsma model and the hierarchical receiver operating characteristic curve model were used to evaluate the diagnostic performance of molecular tests at a 95% confidence interval. A subgroup meta-analysis was performed to explore sources of heterogeneity. RESULTS: Forty-seven articles were identified for qualitative synthesis, of which 23 met the inclusion criteria for meta-analysis. The pooled sensitivities in conventional polymerase chain reaction (PCR) and real-time PCR were 77.52 (59.50-89.01) and 68.43 (54.96-79.39), respectively. The pooled specificities were 98.00 (90.73-99.59) and 98.84 (97.55-99.46), respectively. Ulcer samples had a better performance (sensitivity of 79.88 [69.00-87.62] and specificity of 98.58 [97.25-99.27]), and the major target genes were the polymerase A gene and tpp47 gene. CONCLUSIONS: Our work showed that conventional PCR was more widely used than real-time PCR in the diagnosis of syphilis, and ulcers were the best specimens. Sample types and target genes are factors that may influence the quality of the different tests. These results could provide evidence for further work in the direction of providing a more efficient diagnostic test.

Breast cancer in West Africa: molecular analysis of BRCA genes in early-onset breast cancer patients in Burkina Faso.

BACKGROUND: Breast cancer (BC) is the most commonly diagnosed cancer and the second leading cause of cancer-related deaths among women in Africa after cervical cancer. Even if the epidemiological data are now aligned with those relating to industrialized countries, the knowledge concerning breast cancer in Africa, particularly in Western Africa, still lack clinical data, medical treatments, and the evaluation of genetic and non-genetic factors implicated in the etiology of the disease. The early onset and the aggressiveness of diagnosed breast cancers in patients of African ancestry strongly suggest that the genetic risk factor may be a key component, but so far, very few studies on the impact of germ line mutations in breast cancer in Africa have been conducted, with negative consequences on prevention, awareness and patient management. Through Next Generation sequencing (NGS), we analyzed all of the coding regions and the exon-intron junctions of BRCA1 and BRCA2 genes-the two most important genes in hereditary breast cancer-in fifty-one women from Burkina Faso with early onset of breast cancer with or without a family history. RESULTS: We identified six different pathogenic mutations (three in BRCA1, three in BRCA2), two of which were recurrent in eight unrelated women. Furthermore, we identified, in four other patients, two variants of uncertain clinical significance (VUS) and two variants never previously described in literature, although one of them is present in the dbSNP database. CONCLUSIONS: This is the first study in which the entire coding sequence of BRCA genes has been analyzed through Next Generation Sequencing in Burkinabe young women with breast cancer. Our data support the importance of genetic risk factors in the etiology of breast cancer in this population and suggest the necessity to improve the genetic cancer risk assessment. Furthermore, the identification of the most frequent mutations of BRCA1 and BRCA2 in the population of Burkina Faso will allow the development of an inexpensive genetic test for the identification of subjects at high genetic cancer risk, which could be used to design personalized therapeutic protocols.

Seroprevalence, Genotyping, and Monitoring of Hepatitis C Viral Loads in Patients on Antivirals in Burkina Faso.

INTRODUCTION: Hepatitis C virus (HCV) infection remains a major public health problem worldwide. In Burkina Faso, nearly 720,000 people are living with HCV, and each year about 900 people die from complications of cirrhosis or hepatocellular carcinoma. This study was planned to determine the HCV seroprevalence, characterize circulating genotypes, and monitor HCV viral loads in patients under treatment with antivirals. METHODS: A total of 4,124 individuals and 167 patients in the pre-therapy program were recruited. The "SD Bioline HCV" kit was used for rapid screening of anti-HCV antibodies. Viral load and genotyping were performed in 167 HCV patients on antivirals using the "Iontek HCV Quant" and "Iontek genotyping" kits. RESULTS: Prevalence of HCV was 1.65% (68/4,124), and the median viral load of participants was 5.37 log10/mL (1.32-7.67 log10/mL). Genotype 2 was predominant with a frequency of 86.23% (144/167) and appeared to be more active with higher viral load compared to 13.77% (23/167) for genotype 1 (p < 0.001). After 24 weeks of pan-genotypic direct-acting antivirals, such as sofosbuvir/daclatasvir and sofosbuvir/velpatasvir, the viral loads of all patients became undetectable. CONCLUSION: The responses to antivirals by the circulating genotypes indicate that the results are very satisfactory. Therefore, the prevalence of HCV in the population can be reduced through identification of cases and treatment.

First detection of mutated ERG11 gene in vulvovaginal Candida albicans isolates at Ouagadougou/Burkina Faso.

BACKGROUND: Vulvovaginal candidiasis is an important cause of morbidity among women due to Candida species. In the last decades, resistance to azoles, first-line antifungals has increased. One molecular mechanism of azole resistance by Candida involves mutations in the ERG11 gene encoding lanosterol 14-α-demethylase, the target enzyme. This study was conducted to identify the clinical Candida species associated in vulvovaginal candidiasis; to determine the rate of antifungal resistance among Candida albicans isolates and to determine mutated ERG11 gene at Saint Camille Hospital in Ouagadougou, Burkina Faso. METHODS: Antifungals susceptibility were performed using Kirby-Bauer disk diffusion method. ERG11 gene was detected using conventional PCR in C. albicans isolates resistant to at least one azole. RESULTS: Out of 262 clinical strains isolated, C. albicans accounted for 59.90%, followed by Candida glabrata 27.86%, Candida famata 7.25%, Candida tropicalis 3.05% and Saccharomyces cerevisiae 1.91%. Resistance rate of fluconazole to C. albicans was 59.54%. ERG11 gene was found in 9.79% of 92 C. albicans strains resistant to azoles. CONCLUSIONS: This detection of mutated ERG11 gene in C. albicans is the first in Burkina Faso and may be a cause of azole resistance in recurrent Candida vulvovaginitis.

Cervical cancer in the Hauts-Bassins region of Burkina Faso: Results of a screening campaign by visual inspection with acetic acid (VIA screening in Burkina Faso).

This study was conducted to describe the distribution of precancerous and cancerous lesions of the cervix uteri, enumerated during a mass screening in Burkina Faso. We conducted a cross-sectional study involving 577 women aged 18 to 60 years, carried out from November 23 to December 19, 2013, in the city of Bobo-Dioulasso and in the rural commune of Bama. Regarding the screening results, 89 participants (15.4%) were positive for pre-malignant cervical lesions. Chi-square testing and logistic regression analyses were conducted to identify the likelihood of cervical pre-cancer lesion in the women. Participants less than 29 years old were approximately 3 times more likely to have cervical lesions than participants >39 years. Participants who were parous (1-3 deliveries) and multiparous (four or more deliveries) were approximately 4 times more likely to present with cervical lesions than nulliparous women. Access to screening services is low in the Bobo-Dioulasso region. Further research should be conducted to understand the incidence and distribution of cervical precancerous and cancerous lesions in Burkina Faso.

Population data and genetic structure analysis based on 29 Y-STR loci among the ethnolinguistic groups in Burkina Faso.

Burkina Faso (BF) is a landlocked Sahelian country located in the middle of West Africa. Sixty-three local languages are spoken in BF. Despite this high diversity, the BF population remains poorly investigated, and updated forensic parameters with a large number of Y chromosome short tandem repeats (Y-STRs) are still missing. Herein, 447 DNA samples were typed for a cocktail of 29 Y-STR loci. None of these 447 individuals in total shared a common haplotype. The overall Y-STR haplotypes were successfully uploaded online on the Y-STR Haplotype Reference Database (YHRD) with the accession numbers YA004690 and YA004691. The main haplotype diversity was 0.9999999965, which is much higher than that obtained with 12 Y-STRs in a previous study. Haploid Match Probability for the whole dataset was 0.002237. The phylogenetic analysis of 24 ethnic groups of BF shows that the ethnic group named BISSA is closer to Gur speakers than Mande speakers, where they belong. In addition, genetic structure analysis of 49 African subpopulations sheds light on the fact that geographic proximity turns out to be one of the best predictors of genetic affinity between populations.

Molecular characterization of high-risk human papillomavirus (HR-HPV) in women in Lomé, Togo.

BACKGROUND: The causative agent of cervical cancer referred to as Human papillomavirus (HPV) remains a real public health problem. Many countries in West Africa, such as Togo have no data on the high-risk HPV (HR-HPV) infection and genotypes distribution. In order to fill the knowledge gap in the field in Togo, the main objective of this study was to determine the prevalence of pre-cancerous lesions of the cervix and HR-HPV genotypes among Togolese women. METHODS: Samples were collected from 240 women by introducing a swab in the cervix. Then, the screening of precancerous cervical lesions using the visual inspection with acetic acid and lugol (VIA / VIL) was conducted. The HR-HPV genotypes were characterised by real-time multiplex PCR. RESULTS: Out of 240 women recruited, 128 (53.3%) were infected by HR-HPV. The most common genotypes were HPV 56 (22.7%), followed by HPV 51 (20.3%), HPV 31 (19.5%), HPV 52 (18.8%) and HPV 35 (17.2%). The least common genotypes were HPV 33 (2.3%) and HPV 16 (2.3%). Among the women, 1.3% (3/240) were positive to VIA/VIL. CONCLUSION: This study allowed HR-HPV genotypes to be characterised for the first time in Lomé, Togo. This will help in mapping the HR-HPV genotypes in West Africa.

Glutathione S-transferase M1 and T1 genes deletion polymorphisms and risk of developing essential hypertension: a case-control study in Burkina Faso population (West Africa).

BACKGROUND: Glutathione S-transferases play a key role in the detoxification of persistent oxidative stress products which are one of several risks factors that may be associated with many types of disease processes such as cancer, diabetes, and hypertension. In the present study, we characterize the null genotypes of GSTM1 and GSTT1 in order to investigate the association between them and the risk of developing essential hypertension. METHODS: We conducted a case-control study in Burkina Faso, including 245 subjects with essential hypertension as case and 269 control subjects with normal blood pressure. Presence of the GSTT1 and GSTM1 was determined using conventional multiplex polymerase chain reaction followed by gel electrophoresis analysis. Biochemical parameters were measured using chemistry analyzer CYANExpert 130. RESULTS: Chi-squared test shows that GSTT1-null (OR = 1.82; p = 0.001) and GSTM1-active/GSTT1-null genotypes (OR = 2.33; p <  0.001) were significantly higher in cases than controls; the differences were not significant for GSTM1-null, GSTM1-null/GSTT1-active and GSTM1-null/GSTT1-null (p > 0.05). Multinomial logistic regression revealed that age ≥ 50 years, central obesity, family history of hypertension, obesity, alcohol intake and GSTT1 deletion were in decreasing order independent risk factors for essential hypertension. Analysis by gender, BMI and alcohol showed that association of GSTT1-null with risk of essential hypertension seems to be significant when BMI < 30 Kg/m2, in non-smokers and in alcohol users (all OR ≥ 1.77; p ≤ 0.008). Concerning GSTT1, GSTM1 and cardiovascular risk markers levels in hypertensive group, we found that subjects with GSTT1-null genotype had higher waist circumference and higher HDL cholesterol level than those with GSTT1-active (all p <  0.005), subjects with GSTM1-null genotype had lower triglyceride than those with GSTM1-active (p = 0.02) and subjects with the double deletion GSTM1-null/GSTT1-null had higher body mass index, higher waist circumference and higher HDL cholesterol than those with GSTM1-active/GSTT1-active genotype (all p = 0.01). CONCLUSION: Our results confirm that GSTT1-null genotype is significantly associated with risk of developing essential hypertension in Burkinabe, especially when BMI < 30 Kg/m2, in non-smokers and in alcohol users, and it showed that the double deletion GSTM1-null/GSTT1-null genotypes may influence body lipids repartition.

Pharmacokinetic study of two different rifabutin doses co-administered with lopinavir/ritonavir in African HIV and tuberculosis co-infected adult patients.

BACKGROUND: This study aimed to assess the pharmacokinetic profile of 150 mg rifabutin (RBT) taken every other day (every 48 h) versus 300 mg RBT taken every other day (E.O.D), both in combination with lopinavir/ritonavir (LPV/r), in adult patients with human immunodeficiency virus (HIV) and tuberculosis (TB) co-infection. METHODS: This is a two-arm, open-label, pharmacokinetic, randomised study conducted in Burkina Faso between May 2013 and December 2015. Enrolled patients were randomised to receive either 150 mg RBT EOD (arm A, 9 subjects) or 300 mg RBT EOD (arm B, 7 subjects), both associated with LPV/r taken twice daily. RBT plasma concentrations were evaluated after 2 weeks of combined HIV and TB treatment. Samples were collected just before drug ingestion and at 1, 2, 3, 4, 6, 8, and 12 h after drug ingestion to measure plasma drug concentration using an HPLC-MS/MS assay. RESULTS: The Cmax and AUC0-12h medians in arm A (Cmax = 296 ng/mL, IQR: 205-45; AUC0-12h = 2528 ng.h/mL, IQR: 1684-2735) were lower than those in arm B (Cmax = 600 ng/mL, IQR: 403-717; AUC0-12h = 4042.5 ng.h/mL, IQR: 3469-5761), with a statistically significant difference in AUC0-12h (p = 0.044) but not in Cmax (p = 0.313). No significant differences were observed in Tmax (3 h versus 4 h). Five patients had a Cmax below the plasma therapeutic limit (< 300 ng/mL) in the 150 mg RBT arm, while the Cmax was above this threshold for all patients in the 300 mg RBT arm. Additionally, at 48 h after drug ingestion, all patients had a mycobacterial minimum inhibitory concentration (MIC) above the limit (> 64 ng/mL) in the 300 mg RBT arm, while 4/9 patients had such values in the 150 mg RBT arm. CONCLUSION: This study confirmed that the 150 mg dose of rifabutin ingested EOD in combination with LPV/r is inadequate and could lead to selection of rifamycin-resistant mycobacteria. TRIAL REGISTRATION: PACTR201310000629390, 28th October 2013.

Pharmacokinetics of plasma lopinavir and ritonavir in tuberculosis-HIV co-infected African adult patients also receiving rifabutin 150 or 300 mg three times per week.

BACKGROUND: To evaluate the pharmacokinetic of plasma lopinavir (LPV) and ritonavir (RTV) when co-administered with three times weekly (TPW) rifabutin (RBT) at a dose of either 150 or 300 mg in African tuberculosis (TB) and HIV co-infected adult patients. METHODS: This is a pharmacokinetic study conducted in Ouagadougou among patients treated with a standard dosage of LPV/RTV 400/100 mg twice daily and RBT 150 mg TPW (arm A = 9 patients) or rifabutin 300 mg TPW (arm B = 7 patients) based regimens. Patients were recruited from the Bogodogo and Kossodo district hospitals in Ouagadougou from May 2013 to December 2015. Study inclusion criteria were that the patients were between 18 and 60 years of age, HIV-1 infected with pulmonary tuberculosis confirmed or suspected. Subsequent blood samples for pharmacokinetic monitoring were collected at 1, 2, 3, 4, 6, 8 and 12 h after combined drug ingestion for plasma drug monitoring using HPLC/MS assays. RESULTS: The medians LPV Cmax and Tmax were respectively, 20 µg/mL and 4 h for the RBT 150 mg group (arm A) and 7.7 µg/mL and 3 h for the RBT 300 mg group (arm B). The AUC0-12 of LPV was 111.8 µg h/mL in patients belonging to arm A versus 69.9 µg/mL for those in arm B (p = 0.313). The C0 of LPV was lower than 4 µg/mL in three patients receiving RBT 300 mg. Of note, the RTV plasma concentrations were nearly halved among patients on RBT 300 mg compared to those on lower RBT doses. The AUC0-12 of RTV in arm A was 12.7 µg h/mL versus 6.6 µg h/ml in arm B (p = 0.313). CONCLUSION: In our study, the pharmacokinetic of LPV and RTV was found to be highly variable when coadministrated with RBT 150 mg or 300 mg three times per week. There is a need for specific large study to verify clinical and virological effects of this variation, especially when coadministrated with RBT of 300 mg TPW, and to prevent viral resistance in response to under-dosing of LPV. Trial registration PACTR201310000629390. Registered 28 October 2013, http://www.pactr.org/.

Pharmacological Modulation of Steroid Activity in Hormone-Dependent Breast and Prostate Cancers: Effect of Some Plant Extract Derivatives.

: The great majority of breast and prostate tumors are hormone-dependent cancers; hence, estrogens and androgens can, respectively, drive their developments, making it possible to use pharmacological therapies in their hormone-dependent phases by targeting the levels of steroid or modulating their physiological activity through their respective nuclear receptors when the tumors relapse. Unfortunately, at some stage, both breast and prostate cancers become resistant to pharmacological treatments that aim to block their receptors, estrogen (ER) or androgen (AR) receptors, respectively. So far, antiestrogens and antiandrogens used in clinics have been designed based on their structural analogies with natural hormones, 17-ß estradiol and dihydrotestosterone. Plants are a potential source of drug discovery and the development of new pharmacological compounds. The aim of this review article is to highlight the recent advances in the pharmacological modulation of androgen or estrogen levels, and their activity through their cognate nuclear receptors in prostate or breast cancer and the effects of some plants extracts.