In vivo antimalarial effect of Ananas comosus (L) Merr (Bromeliaceae) fruit peel, and gas chromatography-mass spectroscopy profiling: A possible role for polyunsaturated fatty acid

Purpose: To evaluate the antimalarial effect of Ananas comosus extract and fractions and also to identify the likely bioactive compounds.Method: The fruit peel of the plant was extracted with methanol, and the extract successively fractionated with n-hexane, dichloromethane, ethyl acetate, methanol and water. The n-hexane fraction was further subjected to vacuum liquid chromatography to afford four sub-fractions, one of which was also analyzed using gas chromatography-mass spectroscopy (GC-MS). Plasmodium berghei-infected mice were treated orally with three doses (100, 200 and 400 mg/kg) of the plant extract and a single dose (200 mg/kg) of each of the fractions and sub-fractions in a curative antimalarial model using artemisinin combination therapy (ACT) as the reference drug.Results: The extract exhibited significant (p < 0.001) non-dose dependent parasitemia inhibitory activity in the range of 44.84 to 76.09 %. All fractions displayed inhibitory effect (p < 0.001) in the range of 46.44 to 87.58 % with the dichloromethane fraction displaying the highest effect (87.58 %). The subfractions exhibited significant inhibitory effect (p < 0.001) in the range of 84.14 to 92.54 %. The ACT produced significant (p < 0.001) inhibitory effect of 83.92 %. GC-MS analysis revealed the presence of 17 bioactive compounds, the most abundant of which were linoleic acid and palmitic acid.Conclusion: A. comosus displays strong antimalarial activity which supports the folkloric use of the plant for malarial treatment. A polyunsaturated fatty acid (linoleic acid) was the most abundant phytoconstituent identified. Keywords: Ananas comosus, Antimalarial, Malaria, Pineapple, Plasmodium beighe

Steroid Alkaloids from Holarrhena africana with Strong Activity against Trypanosoma brucei rhodesiense

In our continued search for natural compounds with activity against Trypanosoma brucei, causative agent of human African trypanosomiasis (HAT, "sleeping sickness"), we have investigated extracts from the leaves and bark of the West African Holarrhenaafricana (syn. Holarrhena floribunda; Apocynaceae). The extracts and their alkaloid-enriched fractions displayed promising in vitro activity against bloodstream forms of T. brucei rhodesiense (Tbr; East African HAT). Bioactivity-guided chromatographic fractionation of the alkaloid-rich fractions resulted in the isolation of 17 steroid alkaloids, one nitrogen-free steroid and one alkaloid-like non-steroid. Impressive activities (IC50 in µM) against Tbr were recorded for 3β-holaphyllamine (0.40 ± 0.28), 3α-holaphyllamine (0.37 ± 0.16), 3β-dihydroholaphyllamine (0.67 ± 0.03), N-methylholaphyllamine (0.08 ± 0.01), conessimine (0.17 ± 0.08), conessine (0.42 ± 0.09), isoconessimine (0.17 ± 0.11) and holarrhesine (0.12 ± 0.08) with selectivity indices ranging from 13 to 302. Based on comparison of the structures of this congeneric series of steroid alkaloids and their activities, structure-activity relationships (SARs) could be established. It was found that a basic amino group at position C-3 of the pregnane or pregn-5-ene steroid nucleus is required for a significant anti-trypanosomal activity. The mono-methylated amino group at C-3 represents an optimum for activity. ∆(5,6) unsaturation slightly increased the activity while hydrolysis of C-12β ester derivatives led to a loss of activity. An additional amino group at C-20 engaged in a pyrrolidine ring closed towards C-18 significantly increased the selectivity index of the compounds. Our findings provide useful empirical data for further development of steroid alkaloids as a novel class of anti-trypanosomal compounds which represent a promising starting point towards new drugs to combat human African trypanosomiasis

Chemical constituents of Combretum dolichopetalum: Characterization, antitrypanosomal activities and molecular docking studies

Purpose: To evaluate the in vitro activities of a gallic acid ester and two apigenin flavone glucoside constituents of Combretum dolichopetalum against Trypanosoma brucei brucei s427 (Tbs427) and Trypanosoma congolense IL3000 (Tc-IL3000), and their interactions with a lysosomal papain-like cysteine protease (CP) enzyme in silico.Methods: Anti-trypanosomal activity-guided separation of ethyl acetate fraction using column chromatographic (CC) technique and purification of the CC sub-fractions with semi-preparative HPLC yielded three (1-3) compounds. The structures were characterized based on nuclear magnetic resonance (NMR) spectroscopic analyses and tested for activities against Tbs427 and Tc-IL3000. All the compounds were subjected to molecular docking studies for the inhibition of trypanosomal cathepsin B (TbCatB) CP.Results: An ester (1), a butyl gallate, and two positional isomeric apigenin flavone glucosides (2, 3) were identified. The compounds 2 (vitexin) and 3 (isovitexin) showed low in vitro IC50 against the tested parasites. However, 2 (IC50, 25 μM) was more potent than 3 (IC50, 68 μM) against Tbs427 while both were equipotent (IC50 = 2, 11.5 μM and 3, 10.8 μM) against Tc-IL3000. Compound 1 (butyl gallate) showed higher activity against Tc-IL3000 (IC50 = 0.80 μM) than to Tbs427 (IC50, 2.72 μM). The molecular docking study showed that all the compounds had minimum binding energies with a higher affinity towards the active pocket of TbCatB compared to the controls and native inhibitor (CA074).Conclusion: The relatively high in vitro activities and their strong affinity for TbCatB support the need for further optimization of the compounds towards lead identification against animal trypanosomiasis

Potent antitrypanosomal activities of 3-aminosteroids against African trypanosomes: investigation of cellular effects and of cross-resistance with existing drugs. Molecules

Treatment of animal African trypanosomiasis (AAT) requires urgent need for safe, potent and affordable drugs and this has necessitated this study. We investigated the trypanocidal activities and mode of action of selected 3-aminosteroids against Trypanosoma brucei brucei. The in vitro activity of selected compounds of this series against T. congolense (Savannah-type, IL3000), T. b. brucei (bloodstream trypomastigote, Lister strain 427 wild-type (427WT)) and various multi-drug resistant cell lines was assessed using a resazurin-based cell viability assay. Studies on mode of antitrypanosomal activity of some selected 3-aminosteroids against Tbb 427WT were also carried out. The tested compounds mostly showed moderate-to-low in vitro activities and low selectivity to mammalian cells. Interestingly, a certain aminosteroid, holarrhetine (10, IC50 = 0.045 ± 0.03 µM), was 2 times more potent against T. congolense than the standard veterinary drug, diminazene aceturate, and 10 times more potent than the control trypanocide, pentamidine, and displayed an excellent in vitro selectivity index of 2130 over L6 myoblasts. All multi-drug resistant strains of T. b. brucei tested were not significantly cross-resistant with the purified compounds. The growth pattern of Tbb 427WT on long and limited exposure time revealed gradual but irrecoverable growth arrest at ≥ IC50 concentrations of 3-aminosteroids. Trypanocidal action was not associated with membrane permeabilization of trypanosome cells but instead with mitochondrial membrane depolarization, reduced adenosine triphosphate (ATP) levels and G2/M cell cycle arrest which appear to be the result of mitochondrial accumulation of the aminosteroids. These findings provided insights for further development of this new and promising class of trypanocide against African trypanosomes

Pediatric Bacterial Meningitis Surveillance in Nigeria From 2010 to 2016, Prior to and During the Phased Introduction of the 10-Valent Pneumococcal Conjugate Vaccine.

BACKGROUND: Historically, Nigeria has experienced large bacterial meningitis outbreaks with high mortality in children. Streptococcus pneumoniae (pneumococcus), Neisseria meningitidis (meningococcus), and Haemophilus influenzae are major causes of this invasive disease. In collaboration with the World Health Organization, we conducted longitudinal surveillance in sentinel hospitals within Nigeria to establish the burden of pediatric bacterial meningitis (PBM). METHODS: From 2010 to 2016, cerebrospinal fluid was collected from children <5 years of age, admitted to 5 sentinel hospitals in 5 Nigerian states. Microbiological and latex agglutination techniques were performed to detect the presence of pneumococcus, meningococcus, and H. influenzae. Species-specific polymerase chain reaction and serotyping/grouping were conducted to determine specific causative agents of PBM. RESULTS: A total of 5134 children with suspected meningitis were enrolled at the participating hospitals; of these 153 (2.9%) were confirmed PBM cases. The mortality rate for those infected was 15.0% (23/153). The dominant pathogen was pneumococcus (46.4%: 71/153) followed by meningococcus (34.6%: 53/153) and H. influenzae (19.0%: 29/153). Nearly half the pneumococcal meningitis cases successfully serotyped (46.4%: 13/28) were caused by serotypes that are included in the 10-valent pneumococcal conjugate vaccine. The most prevalent meningococcal and H. influenzae strains were serogroup W and serotype b, respectively. CONCLUSIONS: Vaccine-type bacterial meningitis continues to be common among children <5 years in Nigeria. Challenges with vaccine introduction and coverage may explain some of these finding. Continued surveillance is needed to determine the distribution of serotypes/groups of meningeal pathogens across Nigeria and help inform and sustain vaccination policies in the country

Emergence and spread of two SARS-CoV-2 variants of interest in Nigeria.

Identifying the dissemination patterns and impacts of a virus of economic or health importance during a pandemic is crucial, as it informs the public on policies for containment in order to reduce the spread of the virus. In this study, we integrated genomic and travel data to investigate the emergence and spread of the SARS-CoV-2 B.1.1.318 and B.1.525 (Eta) variants of interest in Nigeria and the wider Africa region. By integrating travel data and phylogeographic reconstructions, we find that these two variants that arose during the second wave in Nigeria emerged from within Africa, with the B.1.525 from Nigeria, and then spread to other parts of the world. Data from this study show how regional connectivity of Nigeria drove the spread of these variants of interest to surrounding countries and those connected by air-traffic. Our findings demonstrate the power of genomic analysis when combined with mobility and epidemiological data to identify the drivers of transmission, as bidirectional transmission within and between African nations are grossly underestimated as seen in our import risk index estimates