Characterization of human papillomavirus genotypes and their coverage in vaccine delivered to Ethiopian women.

Cervical cancer is a significant public health concern in Ethiopia. It is mainly caused by persistent infection with the human papillomaviruses. The aim of this study was to assess the relationship between carcinogenic risk of probable, possible and low risk HPV infection and those of cervical intraepithelial neoplasia (CIN) and cervical cancer. A cross sectional study nested from prospective cohort study was conducted in Bahir Dar, northwest Ethiopia. Statistical analyses were performed using SPSSversion 26.0. HPV-16 was associated with a relatively higher risk of CIN II+, (AOR = 15.42; 95% CI 6.81-34.91). In addition, HPV-52, -18, -53 and -58, were significantly associated with an increased risk of CIN II+, (AOR = 7.38 (1.73-31.54), 5.42 (1.61-18.31), 4.08 (1.53-10.87), and 3.17 (1.00-10.03)), respectively. The current study shows high rate of HPV with predominance of HPV-16, -53, -58, -18, -35, and -52. The quadrivalent and nonavalent vaccine had only covered 27.1% and 45% of the circulating HPV genotypes. Ethiopia may need to consider introduction of nonavalent vaccine into the national public health strategy. Polyvalent vaccine which includes the genotypes not covered by existing approved vaccines should be considered.

Prevalence and associated risk factors of Helicobacter pylori infection in East Africa: a systematic review and meta-analysis.

BACKGROUND: Helicobacter pylori is the main cause of chronic gastritis, peptic ulcer, lymphoma, and gastric cancer in humans. The prevalence and factors associated with H. pylori infection are varied across countries. Thus, a comprehensive review has not been done on prevalence and associated factors in East Africa. Therefore, this systematic review and meta-analysis aimed to estimate the pooled prevalence and identify factors associated with H. pylori infection in East Africa. METHODS: Articles written in English language were retrieved from PubMed, Scopus, and Science Direct. Relevant articles were selected and screened using Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Publication bias was assessed qualitatively and qualitatively using funnel plot symmetry and Egger's test, respectively. Heterogeneity was assessed using the I2 measure. Data were analyzed using Stata software, version 14, and the "metan" command. RESULTS: A total of 231 articles were retrieved from nineteen countries in East Africa. Of these, 70 articles were eligible for the review. The pooled prevalence of H. pylori in East Africa was 50.98% (95% CI: 45.05-56.90). The prevalence of H. pylori infection ranged from 7.7 to 94.5% in East African countries. The highest pooled prevalence was from Sudan (61.3%, 95% CI: 52.6-69.9), and the lowest prevalence was reported from Uganda (40.7%, 95% CI: 33-48.3). Persons with no formal education (OR: 2.03; 95% CI: 1.22-2.83), lack of hand washing habit after toilet (OR: 2.24; 95% CI: 1.45-3.02), having a history of dyspepsia (OR: 2.25; 95% CI: 1.31-3.18), living in rural areas (OR = 1.80; 95% CI: 0.38-3.23), and having unclean water source (OR = 1.5; 95% CI:0.45-3.45) were all associated with higher risk for H. pylori infection. CONCLUSION: More than half of the populations of East African countries were positive for H. pylori infection. Rural residence, source of water, and alcohol consumption were significantly associated with H. pylori infection. Therefore, healthcare workers could provide health education on the aforementioned risk factors, and the government and other stakeholders could improve the source of drinking water in East Africa.

Sero- and Feco-Prevalence of Helicobacter pylori Infection and Its Associated Risk Factors among Adult Dyspeptic Patients Visiting the Outpatient Department of Adet Primary Hospital, Yilmana Densa District, Northwest Ethiopia.

Background: Most gastric cancers in the world are attributed to Helicobacter pylori (H. pylori) infections. The prevalence of H. pylori infection is influenced by socioeconomic status, hygiene, and lifestyle of the population. This study aimed to assess sero- and feco-prevalence of H. pylori infections and its associated risk factors among adult dyspeptic patients visiting the outpatient department of Adet Primary Hospital, Yilmana Densa District, northwest Ethiopia. Methods: A hospital-based cross-sectional study was conducted from February 10, 2022 to April 10, 2022. The study participants were selected using a systematic random sampling technique. The data were collected by pretested questionnaires. Blood and stool specimens were collected from each patient for antibody and H. pylori antigen tests, respectively. The data were analyzed using Statistical Package for Social Science (SPSS) version 26.0. A logistic regression model was used to assess the strength of association between H. pylori positivity and risk factors. Results: The sero- and feco-prevalence of H. pylori infection was 62% and 51.1%, respectively. In those patients who had a positive result with either the antibody (Ab) or antigen (Ag) test, rural residence (AOR = 5.55; 95% CI: 2.34-13.14; p < 0.001), alcohol consumption (AOR = 12.34; 95% CI: 2.29-66.51; p=0.003), having no awareness about H. pylori transmission (AOR = 4.76; 95% CI: 1.86-12.15; p=0.001), using pond/river as a source of drinking water (AOR = 5.22; 95% CI: 1.91-14.27; p=0.001), and open field defecation (AOR = 4.19; 95% CI: 1.67-10.52; p=0.002) were the explanatory risk factors significantly associated with H. pylori infection. Conclusion: This study showed that the prevalence of H. pylori infection was very high. Most cases of gastric cancers are ascribed to H. pylori infection. Therefore, education should be given to communities so as to increase their awareness of the infection and the associated major explanatory risk factors identified in the present study.

Insecticide susceptibility status of Anopheles gambiae (s.l.) in and surrounding areas of Lake Tana, northwest Ethiopia.

BACKGROUND: Vector control is the most effective malaria control and prevention measure. Among these, IRS and LLINs are the most important chemical insecticide interventions used in malaria prevention and control strategies in Ethiopia. However, the long-term effectiveness of these strategies is under threat due to the emergency and spread of insecticide resistance in the principal malaria vector. Therefore, this study was carried out, under standardized laboratory conditions to assess the killing effect of some insecticides against An. gambiae s.l. METHODS: Mosquitoes in late instar larvae and pupae stages were collected from different breeding habitats of the study sites using a soup ladle (350 ml capacity). The immature was reared to adults at optimum temperature and humidity in a field insectary using the WHO protocol. Four insecticides representing three chemical classes were used against adult mosquitoes. These were permethrin, deltamethrin, pirimiphos-methyl and bendiocarb. Susceptibility tests were carried out from September to December 2021 using the WHO standard procedures. Mortality rate, variation, interaction effect and knockdown times (KDT50 and KDT95%) were computed using descriptive statistics, multivariate analysis of variance and log-probit regression model using SPSS version 20 software. RESULTS: Totally, 1300 Anopheles gambiae s.l. were tested to determine the susceptibility status to the four insecticides. Among these, 90.7% of them were susceptible to insecticides, whereas the remaining 9.3% of specimens were resistant to the insecticides. The results of the analysis of variance showed that mortality significantly varied between insecticides (F = 26.06, DF = 3, P < .0001), but not between study locations (F = 1.56, DF = 3, P = 0.212). On the other hand, the mean comparison of dead mosquitoes showed some signs of interaction between bendiocarb and locations, but not other insecticides and locations. CONCLUSIONS: This study revealed that the knockdown times and effectiveness of different insecticides varied in different study sites. Therefore, insecticide resistance information is very essential for concerned bodies to make informed and evidence-based decisions on vector control.

High-risk human papillomavirus genotype distribution among women with gynecology complaints in northwest Ethiopia.

BACKGROUND: Human papillomavirus (HPV) genotypes differ by geographic location. With the advent of HPV vaccination and HPV-based cervical screening tests in Ethiopia, a nationwide dataset on the genotype distribution of HPV among women has paramount importance in the fight against cervical cancer. However, there is limited data in this regard in the northwest part of the country. Therefore, this study aimed to identify the genotype distribution of high-risk HPVs among women presenting with cervical abnormalities. METHODS: A health facility-based cross-sectional study was conducted at Felege Hiwot Comprehensive Specialized Hospital (FHCSH), Bahir Dar-Ethiopia. Women aged ≥ 30 years who visited the hospital gynecology unit from 01 March 2019 to 30 October 2021 were included. Following general and pelvic examinations, a senior gynecologist collected cervical punch biopsies for histopathological examinations and cervical swabs for HR-HPV detection using the Abbott Alinity m system (Abbott Molecular, Des Plaines, IL, USA). Extended genotyping was carried out with the INNO-LiPA HPV Genotyping Extra II assay (INNO-LiPA; Fujirebio Europe, Ghent, Belgium) as per the manufacturer protocols at the Institute of Virology, Leipzig University Hospital, Germany. RESULTS: We included 355 women with a mean age of 46.4 ± 11.4 years. The majority of the participants, 277 (79.4%) were sexually active before the age of 18 years and 180 (51.6%) had multiple sexual partners. Forty-eight (13.5%) of the participants were HIV positive. The proportion of HR-HPV was 53.0% (n = 188; 95%CI: 47.8-58.1%). From these samples, 13 different HR-HPV types with a total of 258 sequences were identified. The detection of HR-HPV increased significantly with an increase in the age of the participants. The predominant identified HR-HPV was HPV16, 50.4% followed by HPV31 (9.7%), HPV33 (8.5%), HPV39, and HPV68 each (5.8%) and HPV18 (4.7%). Of the total HR-HPV-positive women, 23.9% (45/188) were infected with multiple HR-HPV types. All HPV16, HPV18, HPV35, and HPV45 genotypes (as a single or in coinfections) were found to be associated with either high-grade lesions or cervical cancer. CONCLUSIONS: HR-HPV infection was reportedly higher among women in the present study area. Based on our findings, we strongly recommend the nonavalent HPV vaccine for immunization and any HPV-based screening method to take into consideration the predominant genotypes circulating in the country. The role of multiple HPV infections in high-grade cervical lesions entails further study in Ethiopia.

Cervical cancer in Ethiopia: a review of the literature.

BACKGROUND: Cervical cancer is one of the most common malignancies affecting women worldwide with large geographic variations in prevalence and mortality rates. It is one of the leading causes of cancer-related deaths in Ethiopia, where vaccination and screening are less implemented. However, there is a scarcity of literature in the field. Therefore, the objective of this review was to describe current developments in cervical cancer in the Ethiopian context. The main topics presented were the burden of cervical cancer, knowledge of women about the disease, the genotype distribution of Human papillomavirus (HPV), vaccination, and screening practices in Ethiopia. METHODS: Published literature in the English language on the above topics until May 2021 were retrieved from PubMed/Medline, SCOPUS, Google Scholar, and the Google database using relevant searching terms. Combinations of the following terms were considered to retrieve literature; < Cervical cancer, uterine cervical neoplasms, papillomavirus infections, papillomavirus vaccines, knowledge about cervical cancer, genotype distribution of HPV and Ethiopia > . The main findings were described thematically. RESULTS: Cervical cancer is the second most common and the second most deadly cancer in Ethiopia, The incidence and prevalence of the disease is increasing from time to time because of the growth and aging of the population, as well as an increasing prevalence of well-established risk factors. Knowledge and awareness about cervical cancer is quite poor among Ethiopian women. According to a recent report (2021), the prevalence of previous screening practices among Ethiopian women was at 14%. Although HPV 16 is constantly reported as the common genotype identified from different grade cervical lesions in Ethiopia, studies reported different HPV genotype distributions across the country. According to a recent finding, the most common HPV types identified from cervical lesions in the country were HPV-16, HPV-52, HPV-35, HPV-18, and HPV-56. Ethiopia started vaccinating school girls using Gardasil-4™ in 2018 although the coverage is insignificant. Recently emerging reports are in favor of gender-neutral vaccination strategies with moderate coverage that was found superior and would rapidly eradicate high-risk HPVs than vaccinating only girls. CONCLUSIONS: Cervical cancer continues to be a major public health problem affecting thousands of women in Ethiopia. As the disease is purely preventable, classic cervical cancer prevention strategies that include HPV vaccination using a broad genotype coverage, screening using a high precision test, and treating cervical precancerous lesions in the earliest possible time could prevent most cervical cancer cases in Ethiopia. The provision of a focused health education supported by educational materials would increase the knowledge of women about cervical cancer in general and the uptake of cervical cancer prevention and screening services in particular.

Histopathological profile of cervical punch biopsies and risk factors associated with high-grade cervical precancerous lesions and cancer in northwest Ethiopia.

INTRODUCTION: Cervical cancer is an important public health problem in Ethiopia. However, the disease is not well characterized and studied in various parts of the country. This study was designed to describe the histopathological profile of cervical biopsies and to identify risk factors associated with high-grade cervical lesions and cancer (CIN2+C). METHODS: A cross-sectional study was conducted at Felege Hiwot Compressive Specialized Hospital (FHCSH) between 1 March 2019 and 30 October 2021. A structured questionnaire was used to collect data on the participants' demographic, reproductive and gynecologic history. From women presented with different degrees of cervical lesions, a senior gynecologist collected cervical swabs using (Digene HC2 DNA collection device: Qiagen, Hilden, Germany) for detection of high-risk Human papillomaviruses (HR-HPV) and punch biopsy for histopathological examinations. HR-HPVs were detected using the Abbott Alinity m system following the manufacturer protocol at the Institute of Virology, Leipzig University Hospital, Germany. Collected data entered and analyzed using SPSS version 25. A logistic regression model was used for both bivariable & multivariable analysis in order to determine the association between independent variables and CIN2+C. Statistical significance was set at a p-value <0.05. RESULTS: In this study, 335 women were included; the mean age was at 46.5±11.4 years. Most were living in rural settings, 221(66%) and had no formal education, 259 (77.3%). More than half of the participants, 193(57.6%) were unaware of cervical cancer. The prevalence of HIV infection and previous history of cervical screening were 44(13.1%) and 93(27.8%), respectively. HR-HPVs were detected in 178(54.3%) of the participants. The majority of biopsies, 140(41.8%; 95%CI: 36.6-47.1%), were diagnosed as cervical carcinoma. Normal histology, cervicitis, cervical intraepithelial neoplasia (CIN)-1, CIN-2, and CIN-3 accounted for 74(22.1%), 30(9.0%), 40(11.9%), 12(3.6%), and 12(3.6%), respectively. High-grade lesions and cancer (CIN2+C) together accounted 164(49.0%; 95%CI: 43.6-54.2). Cervical cancer increased steadily with the age of the participants (p<0.001) in which women above the age of fifty were approximately four times more likely to develop CIN2+C than the younger ones (AOR: 3.73; 95%CI: 1.80-7.82; p<0.001). Likewise, no screening history in the last five years (AOR: 2.03; 95%CI: 1.05-3.92; p = 0.035) and being infected with HR-HPVs (AOR: 14.23; 95%CI: 7.9-25.64; p<0.001) were found significantly associated with CIN2+C. CONCLUSIONS: The findings of this study revealed that cervical cancer continues to be an important women's health challenge in northwest Ethiopia. Postmenopausal women, who had no screening history within a five-year period and those women who tested positive for HR-HPV need special attention. It is important to increase the awareness of women about cervical cancer and actions for early detection of precancerous lesions should be expanded.

Human papillomavirus genotype distribution in Ethiopia: an updated systematic review.

BACKGROUND: Cervical cancer is caused by infection with high-risk human papillomaviruses (HR-HPVs). It is one of the leading causes of cancer-related deaths in Ethiopia and globally. To develop efficient vaccination and HPV-based cervical cancer screening approaches, data on genotype distribution of HPVs is crucial. Hence, the study was aimed to review HPV genotype distribution in Ethiopia. METHODS: Research articles were systematically searched using comprehensive search strings from PubMed/Medline and SCOPUS. Besides, Google Scholar was searched manually for grey literature. The last search was conducted on 18 August 2021. The first two authors independently appraised the studies for scientific quality and extracted the data using Excel sheet. The pooled HPV genotype distribution was presented with descriptive statistics. RESULTS: We have included ten studies that were reported from different parts of the country during 2005 and 2019. These studies included 3633 women presented with different kinds of cervical abnormalities, from whom 29 different HPV genotypes with a sum of 1926 sequences were reported. The proportion of high-risk, possible/probable high-risk and low-risk HPVs were at 1493 (77.5%), 182 (9.4%) and 195 (10.1%), respectively. Of the reported genotypes, the top five were HPV 16 (37.3%; 95% CI 35.2.1-39.5%), HPV 52 (6.8%; 95% CI 5.8-8.0%), HPV 35 (4.8%; 95% CI 3.9-5.8%), HPV 18 (4.4%; 95% CI 3.5-5.3%) and HPV 56 (3.9%: 95% CI 3.1-4.9%). Some of other HR-HPV groups include HPV 31 (3.8%), HPV 45 (3.5%), HPV 58 (3.1%), HPV 59(2.3%), and HPV 68 (2.3%). Among the high-risk types, the combined prevalence of HPV 16/18 was at 53.7% (95% CI 51.2-56.3%). HPV 11 (2.7%: 95% CI 2.1-3.5%), HPV 42 (2.1%: 95% CI 1.5-2.8%) and HPV 6 (2.1%: 95% CI 1.4-2.7%) were the most common low-risk HPV types. CONCLUSIONS: We noted that the proportion of HR-HPV types was higher and HPV 16 in particular, but also HPV 52, HPV 35 and HPV 18, warrant special attention in Ethiopian's vaccination and HPV based cervical screening program. Additional data from other parts of the country where there is no previous HPV genotype report are needed to better map the national HPV genotypes distribution of Ethiopia.

Lipid droplets and the transcriptome of Mycobacterium tuberculosis from direct sputa: a literature review.

Mycobacterium tuberculosis (Mtb), the main etiology of tuberculosis (TB), is predominantly an intracellular pathogen that has caused infection, disease and death in humans for centuries. Lipid droplets (LDs) are dynamic intracellular organelles that are found across the evolutionary tree of life. This review is an evaluation of the current state of knowledge regarding Mtb-LD formation and associated Mtb transcriptome directly from sputa.Based on the LD content, Mtb in sputum may be classified into three groups: LD positive, LD negative and LD borderline. However, the clinical and evolutionary importance of each state is not well elaborated. Mounting evidence supports the view that the presence of LD positive Mtb bacilli in sputum is a biomarker of slow growth, low energy state, towards lipid degradation, and drug tolerance. In Mtb, LD may serve as a source of chemical energy, scavenger of toxic compounds, prevent destruction of Mtb through autophagy, delay trafficking of lysosomes towards the phagosome, and contribute to Mtb persistence. It is suggest that LD is a key player in the induction of a spectrum of phenotypic and metabolic states of Mtb in the macrophage, granuloma and extracellular sputum microenvironment. Tuberculosis patients with high proportion of LD positive Mtb in pretreatment sputum was associated with higher rate of poor treatment outcome, indicating that LD may have a clinical application in predicting treatment outcome.The propensity for LD formation among Mtb lineages is largely unknown. The role of LD on Mtb transmission and disease phenotype (pulmonary TB vs extra-pulmonary TB) is not well understood. Thus, further studies are needed to understand the relationships between LD positivity and Mtb lineage, Mtb transmission and clinical types.

In vitro anti-proliferative activity of selected nutraceutical compounds in human cancer cell lines.

OBJECTIVE: We investigated the anti-proliferative or cytotoxic activities of five nutraceutical compounds: allyl isothiocyanate, ß-carotene, caffeine, capsaicin, and lupanine that we consume respectively, for example, from mustard seeds, carrot, coffee, pepper, and lupin seeds against cancer cell lines (human colon: HCT 116 p53 wild type, HCT 116 p53-/- and lymphoblastic: CEM/CCRF, CEM/ADR5000). RESULT: Out of the five compounds tested in vitro, capsaicin and ß-carotene were more cytotoxic than the other three compounds against the four cancer cell lines. The most potent nutraceutical compound was capsaicin and it exerted its highest cytotoxicity against HCT 116 p53-/- with IC50 value of 19.67 ± 0.06 µM. It is worth considering capsaicin for further development of anticancer drug against both colon and leukemia cancer types.

Prevalence of intestinal parasitic infections and associated risk factors among pregnant women attending antenatal care center at Felege Hiwot Referral Hospital, northwest Ethiopia.

BACKGROUND: Parasitic infections affect tens of millions of pregnant women worldwide, and directly or indirectly lead to a spectrum of adverse maternal and fetal/placental effects. The objective of this study was to assess the prevalence of intestinal parasite infections and associated risk factors among pregnant women attending antenatal care center in Felege Hiwot Referral Hospital, Bahir Dar city, northwest Ethiopia. METHODS: A cross-sectional hospital based study was conducted from November 2013 to January 2014 among 384 pregnant women. Stool samples were examined for the presence of trophozoites, cysts, oocysts, and ova using direct, formal-ether sedimentation, and modified Ziehl-Neelsen techniques. RESULTS: An overall prevalence of 31.5 % intestinal parasite infections was recorded. Eight different species of intestinal parasites were found: two protozoan and six helminth species. The highest prevalence was due to Giardia lamblia (13.3 %) followed by Entamoeba histolytica/dispar (7.8 %), hookworm (5.5 %), Ascaris lumbricoides (2.9 %), Schistosoma mansoni (2.9 %), Strongyloides stercoralis (1.6 %), Taenia spp. (0.8 %), and Hymenolepis nana (0.3 %). CONCLUSIONS: A relatively high prevalence of intestinal parasite infections was observed among pregnant women. Routine stool examination and provision of health education are required for early medical intervention that would affect the pregnant mothers and their foetuses.

Prevalence of intestinal protozoan infections among individuals living with HIV/AIDS at Felegehiwot Referral Hospital, Bahir Dar, Ethiopia.

BACKGROUND: HIV infection continues to pose a serious challenge to global health by predisposing patients to opportunistic infections. A cross-sectional study was conducted from December 2012 to February 2013 to assess the enteric protozoan infection status among individuals living with HIV/AIDS in Felegehiwot Referral Hospital, Bahir Dar, northwest Ethiopia. METHODS: Stool specimens from 399 HIV-positive individuals were examined for the presence of trophozoites, cysts, and oocysts using direct wet mount, formol-ether sedimentation and modified Ziehl-Neelsen techniques. In addition, CD4+ T-cell counts were measured to evaluate the immune status of the study subjects. RESULTS: An overall prevalence of 30.6% enteric protozoan infections was recorded. Pre-ART (antiretroviral treatment) individuals were more infected than patients on ART, although this was not statistically significant (p>0.05). The highest prevalence of enteric protozoan infection was due to Entamoeba histolytica/E. dispar (19.3%), followed by Cryptosporidium spp (5.8%), Giardia lamblia (4.3%), and Isospora belli (1.3%). A CD4+ T-cell count of <200 cells/µl and status of being diarrhoeic were significantly associated with the overall prevalence of enteric protozoan infection. CONCLUSIONS: A relatively high prevalence of enteric protozoan infection was observed among individuals living with HIV/AIDS. Routine stool and CD4+ T-cell examinations should be conducted to monitor the status of HIV/AIDS patients.

Anti-infective and cytotoxic properties of Bupleurum marginatum.

BACKGROUND: Bupleurum marginatum Wall. ex DC (Apiaceae) is a perennial herb widely used in traditional Chinese and Kampo medicine for the treatment of various infectious diseases. The biological activities of B. marginatum have not been fully investigated. This study aims to investigate the antitrypanosomal, antimicrobial and antiviral activities of methanol (ME) and dichloromethane (DCM) extracts of B. marginatum aerial parts and the ability of both extracts to inhibit the growth of different cancer cell lines. METHODS: Phytochemical characterization of the extracts was performed by LC-MS profiling. The antitrypanosomal activity was evaluated using the resazurin method. The antimicrobial activity was assessed using agar diffusion and microdilution methods, and the minimum inhibitory concentration (MIC) values were determined. The antiviral activity was determined for 6.25, 12.5, and 50 µg/mL doses using a plaque reduction assay. Cytotoxicity was investigated in eight cancer cell lines (Caco-2, CCL-81, CCRF-CEM, COS-7, HL-60, MIA PaCa-2, MCF-7, and PANC-1) using the MTT assay and the caspase 3/7 activity was determined over the range of 62.5-1000 µg/mL. RESULTS: Phytochemical analyses resulted in the characterization of 15 components, mainly flavonoids and lignans. The DCM extract showed significant antitrypanosomal activity (IC50: 36.21 µg/mL) and moderate activity against Streptococcus pyogenes (MIC value: 0.25 mg/mL). At a dose of 12.5 µg/mL, the DCM extract inhibited 73.6% of the plaque production by hepatitis A virus. CCRF-CEM cells were the most sensitive to both extracts (IC50: 12.5-22.7 µg/mL). The cytotoxicity was mediated by induction of apoptosis (19-fold increase in the cellular caspase 3/7 level after treatment with the DCM extract at 1 mg/mL). CONCLUSIONS: ME and DCM extract of B. marginatum showed anti-infective and antiproliferative effects.

Biological activities of xanthatin from Xanthium strumarium leaves.

The objective of the present work was to evaluate the biological activities of the major bioactive compound, xanthatin, and other compounds from Xanthium strumarium (Asteraceae) leaves. Inhibition of bloodstream forms of Trypanosoma brucei brucei and leukaemia HL-60 cell proliferation was assessed using resazurin as a vital stain. Xanthatin was found to be the major and most active compound against T. b. brucei with an IC(50) value of 2.63 µg/mL and a selectivity index of 20. The possible mode of action of xanthatin was further evaluated. Xanthatin showed antiinflammatory activity by inhibiting both PGE(2) synthesis (24% inhibition) and 5-lipoxygenase activity (92% inhibition) at concentrations of 100 µg/mL and 97 µg/mL, respectively. Xanthatin exhibited weak irreversible inhibition of parasite specific trypanothione reductase. Unlike xanthatin, diminazene aceturate and ethidium bromide showed strong DNA intercalation with IC(50) values of 26.04 µg/mL and 44.70 µg/mL, respectively. Substantial induction of caspase 3/7 activity in MIA PaCa-2 cells was observed after 6 h of treatment with 100 µg/mL of xanthatin. All these data taken together suggest that xanthatin exerts its biological activity by inducing apoptosis and inhibiting both PGE(2) synthesis and 5-lipoxygenase activity thereby avoiding unwanted inflammation commonly observed in diseases such as trypanosomiasis.

Trypanocidal and cytotoxic effects of 30 Ethiopian medicinal plants.

Trypanocidal and cytotoxic effects of traditionally used medicinal plants of Ethiopia were evaluated. A total of 60 crude plant extracts were prepared from 30 plant species using CH2Cl2 and MeOH. Effect upon cell proliferation by the extracts, for both bloodstream forms of Trypanosoma brucei brucei and human leukaemia HL-60 cells, was assessed using resazurin as vital stain. Of all CH2Cl2 and MeOH extracts evaluated against the trypanosomes, the CH2Cl2 extracts from five plants showed trypanocidal activity with an IC50 value below 20 microg/mL: Dovyalis abyssinica (Flacourtiaceae), IC50 = 1.4 microg/mL; Albizia schimperiana (Fabaceae), IC50 = 7.2 microg/mL; Ocimum urticifolium (Lamiaceae), IC50 = 14.0 microg/mL; Acokanthera schimperi (Apocynaceae), IC50 = 16.6 microg/mL; and Chenopodium ambrosioides (Chenopodiaceae), IC50 = 17.1 microg/mL. A pronounced and selective killing of trypanosomes with minimal toxic effect on human cells was exhibited by Dovyalis abyssinica (CH2Cl2 extract, SI = 125.0; MeOH extract, SI = 57.7) followed by Albizia schimperiana (CH2Cl2 extract, SI = 31.3) and Ocimum urticifolium (MeOH extract, SI = 16.0). In conclusion, the screening of 30 Ethiopian medicinal plants identified three species with good antitrypanosomal activities and low toxicity towards human cells. Dovyalis abyssinica might be a promising candidate for phytotherapy of trypanosomiasis.

Biological activity of the essential oil of Kadsura longipedunculata (Schisandraceae) and its major components.

OBJECTIVES: The aim was to determine the chemical composition of the essential oil of Kadsura longipedunculata and the biological activity of the oil and its major components. METHODS: The essential oil from stem bark of Kadsura longipedunculata was analysed by capillary gas chromatography (GLC/FID) and gas chromatography-mass spectrometry (GLC/MS). The ability of the oil to reduce diphenylpicrylhydrazine (DPPH(*)) was used to evaluate the antioxidant activity. Inhibition of both lipoxygenase and prostaglandin E(2) was used to assess the anti-inflammatory activity. Antimicrobial activity was studied in vitro against a range of bacteria and fungi using diffusion and microdilution methods. Inhibition of trypanosome proliferation was assessed using resazurin as vital stain. The in-vitro cytotoxicity of the essential oil on six human cancer cell lines (HepG2, MIA PaCa-2, HeLa, HL-60, MDA-MB-231 and SW-480) was examined using the MTT assay. KEY FINDINGS: Fifty compounds, representing 97.63% of total oil, were identified. delta-Cadinene (21.79%), camphene (7.27%), borneol (6.05%), cubenol (5.12%) and delta-cadinol (5.11%) were found to be the major components of the oil. The oil exerted a good antimicrobial activity against all Gram-positive bacteria tested, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis. Streptococcus pyogenes and S. agalactiae were the most sensitive bacteria with a minimal inhibitory concentration (MIC) of 60 microg/ml oil. The essential oil showed a moderate fungicidal activity against yeasts, but it did not show any activity against Gram-negative bacteria. The essential oil showed a good trypanocidal activity in Trypanosoma b. brucei with an IC50 value of 50.52 +/- 0.029 microg/ml. Radical scavenging activity had an IC50 value of 3.06 +/- 0.79 mg/ml. 5-Lipoxygenase inhibition (IC50 = 38.58 microg/ml) and prostaglandin E(2) production inhibition (28.82% at 25 microg/ml) accounted for anti-inflammatory activity of the oil. The oil exhibited some degree of cytotoxic activity against MIA PaCa-2, HepG-2 and SW-480 cell lines with IC50 values of 133.53, 136.96 and 136.62 microg/ml, respectively. The oil increased caspase 3/7 activity (an indicator of apoptosis) 2.5-4 fold in MIA Paca-2 cells. Camphene and borneol did not show antioxidant activity. However, both compounds exhibited some degree of antimicrobial, trypanocidal, anti-inflammatory and cytotoxic activity. CONCLUSIONS: This investigation provided evidence for, and confirmed the efficacy of, K. longipedunculata, a traditionally used Chinese medicinal plant for the treatment of inflammation and infection.

Screening of some Tanzanian medicinal plants for their trypanocidal and cytotoxic activities.

The objective of the present study was to evaluate in vitro antitrypanosomal and cytotoxic activities of crude extracts of 20 traditionally used medicinal plants of Tanzania. A total of 40 extracts (dichloromethane and methanol) were screened for antiproliferative activity of bloodstream form of T. b. brucei and human leukaemia HL-60 cell. Inhibition of cell proliferation was assessed using resazurin as vital stain. Of the 40 extracts tested, the dichloromethane extract from bark of Warburgia salutaris (Canellaceae) exhibited the most potent antitrypanosomal activity with an IC(50) value of 10.68 microg/ml. A dichloromethane extract from Lannea stuhlmannii (Anacardiaceae) was found to be the most cytotoxic extract against HL-60 (IC(50) = 27.15 microg/ml). Out of the 20 plants tested, 5 plants exhibited trypanocidal activity with IC(50) values below 20 microg/ml. These 5 plants: Entandrophragma bussei (Meliaceae), Securidaca longepedunculata (Polygalaceae), Warburgia salutaris (Canellaceae), Zanha africana (Sapindaceae) and Zanthoxylum chalybeum (Rutaceae) could therefore serve as sources of lead compounds for treatment of trypanosomiasis.

Antitrypanosomal and cytotoxic activities of pyrrolizidine alkaloid-producing plants of Ethiopia.

OBJECTIVES: The objective was to determine the in-vitro effect of extracts from 19 Ethiopian plant species and four pure pyrrolizidine alkaloids on bloodstream forms of Trypanosoma brucei brucei and human leukaemia HL-60 cells. METHODS: Crude plant extracts were prepared using methanol and dichloromethane. The alkaloidal extracts from Solanecio angulatus flowers were prepared with and without zinc reduction using the acid-base extraction method. Cell proliferation inhibitory activity of the extracts and compounds was assessed using Alamarblue. KEY FINDINGS: The most active extract was the dichloromethane extract of Solanecio angulatus flowers, with an IC50 value of 12.17 microg/ml. The best selectivity index (SI > 41.08) was obtained for the same extract determined with HL-60 cells. The reduced alkaloidal extract prepared from S. angulatus flowers and after acid-base extraction showed more antitrypanosomal activity than unreduced alkaloidal extract with an IC50 value of 14.35 microg/ml and with a selectivity index of 12.23. The second most active extract was the dichloromethane extract of Crotalaria phillipsiae twigs with an IC50 value of 12.67 microg/ml and a selectivity index of 34.35. Most of the other extracts tested showed moderate antitrypanosomal activities to variable extents. Among the four pure pyrrolizidine alkaloids tested, senecionine showed moderate antitrypanosomal activity with an IC50 value of 41.78 microg/ml. CONCLUSIONS: Solanecio angulatus (flowers) and Crotalaria phillipsiae (twigs) could serve as sources of novel trypanocidal compounds for the treatment of trypanosomiasis.