Dominic Edoh

Epidemiology of Hookworm Infection in Kintampo North Municipality, Ghana: Patterns of Malaria Coinfection, Anemia, and Albendazole Treatment Failure

A cross-sectional pilot study of hookworm infection was carried out among 292 subjects from 62 households in Kintampo North, Ghana. The overall prevalence of hookworm infection was 45%, peaking in those 11-20 years old (58.5%). In children, risk factors for hookworm infection included coinfection with malaria and increased serum immunoglobulin G reactivity to hookworm secretory antigens. Risk factors for infection in adults included poor nutritional status, not using a latrine, not wearing shoes, and occupation (farming). Although albendazole therapy was associated with an overall egg reduction rate of 82%, 37 subjects (39%) remained infected. Among those who failed therapy, treatment was not associated with a significant reduction in egg excretion, and nearly one-third had higher counts on repeat examination. These data confirm a high prevalence of low-intensity hookworm infection in central Ghana and its association with poor nutritional status. The high rate of albendazole failure raises concern about emerging resistance.

Anti-Trypanosomal Activity of Diarylheptanoids Isolated from the Bark of Alnus japonica

The crude extract of Alnus japonica bark exhibited a strong effect on the growth of Trypanosoma brucei. Subsequent chromatographic separation resulted in the isolation of two novel diarylheptanoids, known as alnuside C (2) and alnuside D (3), and three known compounds, 1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-heptan-3(R)-O-β-D-glucopyranoside (1), oregonin (4) and hirsutanone (5). The structures of the isolates were elucidated based on the use of extensive spectroscopic and chemical methods. Among the isolated diarylheptanoids, oregonin (4) (a major component of plant bark) and hirsutanone (5) exhibited potent in vitro inhibitory activity against T. brucei growth in the bloodstream with IC50 values of 1.14 and 1.78 μM, respectively. We confirmed that oregonin (4) and hirsutanone (5) were not toxic to human normal skin fibroblast cells (NB1RGB) and colon cancer cells (HCT-15) at a concentration of 50 μM; however, lower levels of toxicity were observed for leukemia cells. To determine the structure activity relationships of the isolated components, we performed Conformation Search and found that the 3-oxo function of the heptane chain in the diarylheptanoid molecule is required for their trypanocidal activity.

Procyanidin trimer C1 derived from Theobroma cacao reactivates latent human immunodeficiency virus type 1 provirus

Despite remarkable advances in combination antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) infection remains incurable due to the incomplete elimination of the replication-competent virus, which persists in latent reservoirs. Strategies for targeting HIV reservoirs for eradication that involves reactivation of latent proviruses while protecting uninfected cells by cART are urgently needed for cure of HIV infection. We screened medicinal plant extracts for compounds that could reactivate the latent HIV-1 provirus and identified a procyanidin trimer C1 derived from Theobroma cacao as a potent activator of the provirus in human T cells latently infected with HIV-1. This reactivation largely depends on the NF-κB and MAPK signaling pathways because either overexpression of a super-repressor form of IκBα or pretreatment with a MEK inhibitor U0126 diminished provirus reactivation by C1. A pan-PKC inhibitor significantly blocked the phorbol ester-induced but not the C1-induced HIV-1 reactivation. Although C1-induced viral gene expression persisted for as long as 48 h post-stimulation, NF-κB-dependent transcription peaked at 12 h post-stimulation and then quickly declined, suggesting Tat-mediated self-sustainment of HIV-1 expression. These results suggest that procyanidin C1 trimer is a potential compound for reactivation of latent HIV-1 reservoirs.

High Plasma Levels of Soluble Intercellular Adhesion Molecule (ICAM)-1 Are Associated with Cerebral Malaria

Background Cerebral malaria (CM) is responsible for most of the malaria-related deaths in children in sub-Saharan Africa. Although, not well understood, the pathogenesis of CM involves parasite and host factors which contribute to parasite sequestration through cytoadherence to the vascular endothelium. Cytoadherence to brain microvasculature is believed to involve host endothelial receptor, CD54 or intercellular adhesion molecule (ICAM)-1, while other receptors such as CD36 are generally involved in cytoadherence of parasites in other organs. We therefore investigated the contributions of host ICAM-1 expression and levels of antibodies against ICAM-1 binding variant surface antigen (VSA) on parasites to the development of CM. Methodology/Principal Findings Paediatric malaria patients, 0.5 to 13 years were recruited and grouped into CM and uncomplicated malaria (UM) patients, based on well defined criteria. Standardized ELISA protocol was used to measure soluble ICAM-1 (sICAM-1) levels from acute plasma samples. Levels of IgG to CD36- or ICAM-1-binding VSA were measured by flow cytometry during acute and convalescent states. Wilcoxon sign rank-test analysis to compare groups revealed association between sICAM-1 levels and CM (p<0.0037). Median levels of antibodies to CD36-binding VSA were comparable in the two groups at the time of admission and 7 days after treatment was initiated (p>0.05). Median levels of antibodies to CD36-binding VSAs were also comparable between acute and convalescent samples within any patient group. Median levels of antibodies to ICAM-1-binding VSAs were however significantly lower at admission time than during recovery in both groups. Conclusions/Significance High levels of sICAM-1 were associated with CM, and the sICAM-1 levels may reflect expression levels of the membrane bound form. Anti-VSA antibody levels to ICAM-binding parasites was more strongly associated with both UM and CM than antibodies to CD36 binding parasites. Thus, increasing host sICAM-1 levels were associated with CM whilst antibodies to parasite expressing non-ICAM-1-binding VSAs were not.

Antitrypanosomal Activities and Mechanisms of Action of Novel Tetracyclic Iridoids from Morinda lucida Benth.

ABSTRACT Trypanosoma brucei parasites are kinetoplastid protozoa that devastate the health and economic well-being of millions of people in Africa through the disease human African trypanosomiasis (HAT). New chemotherapy has been eagerly awaited due to severe side effects and the drug resistance issues plaguing current drugs. Recently, there has been an emphasis on the use of medicinal plants worldwide. Morinda lucida Benth. is a popular medicinal plant widely distributed in Africa, and several research groups have reported on the antiprotozoal activities of this plant. In this study, we identified three novel tetracyclic iridoids, molucidin, ML-2-3, and ML-F52, from the CHCl3 fraction of M. lucida leaves, which possess activity against the GUTat 3.1 strain of T. brucei brucei. The 50% inhibitory concentrations (IC50) of molucidin, ML-2-3, and ML-F52 were 1.27 μM, 3.75 μM, and 0.43 μM, respectively. ML-2-3 and ML-F52 suppressed the expression of paraflagellum rod protein subunit 2, PFR-2, and caused cell cycle alteration, which preceded apoptosis induction in the bloodstream form of Trypanosoma parasites. Novel tetracyclic iridoids may be promising lead compounds for the development of new chemotherapies for African trypanosomal infections in humans and animals.

The Ethanolic Leaf Extract of Alchornea cordifolia (Schum. & Thonn.) Muell. Arg Inhibits the Development of Dyslipidaemia and Hyperglycaemia in Dexamethasone-Induced Diabetic Rats -

Article history: Received on: 16/06/2015 Revised on: 10/07/2015 Accepted on: 03/08/2015 Available online: 27/09/2015 Poor lipid and glucose regulation increases the risk for the development of major cardiovascular diseases and other organ damage. The study evaluated the serum glucose and lipid lowering effects of the 70% ( v /v) ethanolic leaf extract of Alchornea cordifolia (ALC) using the dexamethasone-induced diabetic rat model. Thirty six female Sprague-Dawley rats (180-200g; n=6) were rendered hyperglycaemic with dexamethasone (10 mg/kg, sc) once daily for 8 days except the normal control. Each group received either normal saline 0.5 ml/rat, ALC (250 mg/kg, p.o. or 500 mg/kg, p.o.), glibenclamide (5 mg/kg, p.o.) or atorvastatin (5mg/kg, p.o.) as treatment once daily for 8 days. Fasting blood glucose (FBS) readings were recorded at baseline, day 4, 6 and 9. Blood was collected for the estimation of serum triglycerides (TG), total cholesterol (TC), low density lipoproteins (LDL), very low density lipoproteins (VLDL) and high density lipoprotein (HDL) on day 9. The diabetic control group had significantly raised FBS levels (8.20 ± 1.04 mmol/l; ***p<0.001). Glibenclamide (5.20 ± 0.29; ***p<0.001) and the extracts [(ALC 250 mg/kg, p.o.; (5.35 ± 0.95 mmol/l); *p<0.05); ALC 500 mg/kg, p.o.; (5.98 ± 1.12 mmol/l); *p<0.05)] prevented an increase in FBS level. The herbal extracts also reduced the level of serum lipids of rats treated. The 70% ( v /v) ethanolic leaf extract of Alchornea cordifolia has some potential for use in lipid and glucose control.

In vitro antiprotozoan activity and mechanisms of action of selected Ghanaian medicinal plants against Trypanosoma, Leishmania, and Plasmodium parasites: Anti-protozoan activity of selected Ghanaian medicinal plants and mechanisms of action

Trypanosomiasis, leishmaniasis, and malaria are protozoan infections of public health importance with thousands of new cases recorded annually. Control of these infection(s) with existing chemotherapy is limited by drug toxicity, lengthy parenteral treatment, affordability, and/or the emergence of resistant strains. Medicinal plants on the other hand are used in the treatment of various infectious diseases although their chemical properties are not fully evaluated. In this study, we screened 112 crude extracts from 72 selected Ghanaian medicinal plants for anti‐Trypanosoma, anti‐Leishmania, and anti‐Plasmodium activities in vitro and investigated their mechanisms of action. Twenty‐three extracts from 20 plants showed significant antiprotozoan activity against at least 1 of 3 protozoan parasites screened with IC50 values less than 20 μg/ml. Eleven extracts showed high anti‐Trypanosoma activity with Bidens pilosa whole plant and Morinda lucida leaf extracts recording the highest activities. Their IC50 (selectivity index [SI]) values were 5.51 μg/ml (35.00) and 5.96 μg/ml (13.09), respectively. Nine extracts had high anti‐Leishmania activity with Annona senegalensis and Cassia alata leaf extracts as the most active. Their IC50 (SI) values were 10.8 μg/ml (1.50) and 10.1 μg/ml (0.37), respectively. Six extracts had high anti‐Plasmodium activity with the leaf and stem‐bark extracts of Terminalia ivorensis recording the highest activity. Their IC50 (SI) values were 7.26 μg/ml (129.36) and 17.45 μg/ml (17.17), respectively. Only M. lucida at 25 μg/ml induced significant apoptosis‐like cell death in Trypanosoma parasites. Anti‐Leishmania active extracts induced varying morphological changes in Leishmania parasites such as multiple nuclei and/or kinetoplast, incomplete flagella division, or nuclear fragmentation. Active extracts may be potential sources for developing new chemotherapy against these infections.

Antioxidant and antimicrobial capacities of ethanolic extract of Pergularia daemia leaves: a possible substitute in diabetic management.

Abstract Background: The leaves of Pergularia daemia Forsk (family Asclepidaceae) provide alternative plant-based treatments for the management of diabetes mellitus and diarrhoea in both humans and indigenous poultry species like the Guinea fowls (Numida meleagris). However, no scientific investigations to validate its usefulness in Ghana have been established. This study therefore sought to investigate the anti-hyperglycaemic activity of the 70 % ethanolic extract of P. daemia using streptozotocin (STZ)-induced diabetic male Sprague–Dawley rats. Additionally, the antioxidant and antimicrobial properties of the extract were investigated. Methods: The total phenolic content, total flavonoids content, radical scavenging activity and reducing power assays were estimated using Folin–Ciocalteu method, aluminium chloride colorimetric assay, Fe3+ reduction assay and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays, respectively. Results: The results showed that P. daemia extract caused anti-hyperglycaemic activity in the STZ-induced rats at doses of 30, 60 and 90 mg/kg body weight with significant reduction in blood glucose levels. The phytosterols, saponins, phenols, alkaloids, tannins and triterpenes found in the extract may be responsible for the observed anti-hyperglycaemia and antioxidant activities. The extract also showed antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus subtilis. Conclusions: These findings justify the folkloric use of P. daemia as an anti-diabetic and antibacterial agents for susceptible species.

Borassus aethiopum, A Potential Medicinal Source of Antioxidants, Anti-Inflammatory and Antimicrobial Agents

Background: Borassus aethiopum Mart (Family Arecaceae), commonly known as the African Fan Palm, is a tropical plant species found widely across Africa, and used globally for both medicinal and non-medicinal purposes. In this study, the anti-oxidant, anti-microbial and anti-inflammatory activities of an ethanolic extract of the fruit of Borassus aethiopum was investigated. Methods: The Carrageenan induced foot edema model in chicks was used to investigate the anti-inflammatory activity of an ethanolic extract of the seed endocarp cotyledon. For the anti-oxidant activity determination, three assays were employed; namely, the total anti-oxidant capacity assay, the 2, 2-diphenyl- 1-picrylhydrazyl (DPPH) scavenging assay and the Folin-Ciocalteau’s assay for total phenols. For the anti-microbial activity, the agar diffusion method was used. Phytochemical analysis to determine the types of secondary metabolites present was also conducted on the plant extract. Results: The phytochemical screening showed the presence of alkaloid, tannins, saponins, steroids, carbohydrates triterpenoids and phenols. A dose dependent reduction in edema was observed when the extract was compared with Diclofenac and Dexamethasone. The extract had an EC50 of 13.49 µg/ml DPPH scavenging activity, which is excellent when compared to the reference ascorbic acid of 140.00 µg/ml. Thus the extract was about 10 times more potent than the ascorbic acid. Conclusion: The anti-microbial assay revealed activity against the gram positive bacteria Staphylococcus aureus and Bacillus subtilis. The results obtained showed that Borassus aethiopum has anti-inflammatory and significant anti-oxidant properties, which are dose and concentration dependent respectively.

High Levels of IL-10 and CD4+CD25hi+ Treg Cells in Endemic Burkitt’s Lymphoma Patients

Background: The interplay between Epstein-Barr virus infection, malaria, and endemic Burkitt’s Lymphoma is not well understood. Reports show diminished EBV-specific Th1 responses in children living in malaria endemic areas and deficiency of EBNA1-specific IFN-γ T cell responses in children with endemic Burkitt’s Lymphoma (eBL). This study, therefore, examined some factors involved in the loss of EBNA-1-specific T cell responses in eBL. Methods: T-cell subset frequencies, activation, and IFN-γ- or IL-4-specific responses were analyzed by flow-cytometry. Plasma cytokine levels were measured by ELISA. Results: CD4+ and CD8+ cells in age- and sex-matched healthy controls (n = 3) expressed more IFN-γ in response to all immunostimulants than in pediatric endemic BL (eBL) patients (n = 4). In healthy controls, IFN-γ expression was higher than IL-4 expression, whereas in eBL patients the expression of IL-4 by CD4+ cells to EBNA-1 was slightly higher than IFN-γ. Moreover, the blood levels of TNF-α was significantly lower (p = 0.004) while IL-10 was significantly higher (p = 0.038), in eBL patients (n = 21) compared to controls (n = 16). Additionally, the frequency of CD4+CD25hi+ T cells was higher in both age-matched acute uncomplicated malaria (n = 26) and eBL (n = 14) patients compared to healthy controls (n = 19; p = 0.000 and p = 0.027, respectively). Conclusion: The data suggest that reduced Th1 response in eBL might be due to increased levels of IL-10 and T reg cells.