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

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.     

Genetic variants on 15q25.1, smoking, and lung cancer: an assessment of mediation and interaction

Genome-wide association studies have identified variants on chromosome 15q25.1 that increase the risks of both lung cancer and nicotine dependence and associated smoking behavior. However, there remains debate as to whether the association with lung cancer is direct or is mediated by pathways related to smoking behavior. Here, the authors apply a novel method for mediation analysis, allowing for gene-environment interaction, to a lung cancer case-control study (1992-2004) conducted at Massachusetts General Hospital using 2 single nucleotide polymorphisms, rs8034191 and rs1051730, on 15q25.1. The results are validated using data from 3 other lung cancer studies. Tests for additive interaction (P = 2 × 10(-10) and P = 1 × 10(-9)) and multiplicative interaction (P = 0.01 and P = 0.01) were significant. Pooled analyses yielded a direct-effect odds ratio of 1.26 (95% confidence interval (CI): 1.19, 1.33; P = 2 × 10(-15)) for rs8034191 and an indirect-effect odds ratio of 1.01 (95% CI: 1.00, 1.01; P = 0.09); the proportion of increased risk mediated by smoking was 3.2%. For rs1051730, direct- and indirect-effect odds ratios were 1.26 (95% CI: 1.19, 1.33; P = 1 × 10(-15)) and 1.00 (95% CI: 0.99, 1.01; P = 0.22), respectively, with a proportion mediated of 2.3%. Adjustment for measurement error in smoking behavior allowing up to 75% measurement error increased the proportions mediated to 12.5% and 9.2%, respectively. These analyses indicate that the association of the variants with lung cancer operates primarily through other pathways.     

Effect of Community-Based Functional Aerobic Training on Motor Performance and Quality of Life of Children with Spastic Cerebral Palsy

BackgroundEfficacies of community-based exercise programmes have been well reported, but there is scarce information on the expediency of community-based rehabilitation in a society where many children with disabilities live in poorly resourced settings with extremely limited rehabilitative services. This study investigated the effects of community-based functional aerobic exercise (CBFAE) on gross motor function, walking distance, and quality of life of children with cerebral palsy (CP).MethodsQuasi-experimental design was used. Children with gross motor function classification system (GMFCS) levels I – II participated in eight weeks CBFAE training four times/week, 50 minutes/day at 40–80% maximum heart rate. Gross motor function (GMF), walking distance and quality of life were assessed pre and post CBFAE training.ResultsSignificant improvement was observed in GMF (Dstanding) (8.2%, P=.000), GMF (E-walking + running+ jumping (5.12%, P=.004), walking distance (6.09%, P=.009). Higher significant positive effects of CBFAE were observed in Social wellbeing and acceptance (107.10%, P=.000), and participation and physical health (105.04%, P=.005) by children parent proxy. Self-reported results showed that for CBFAE, significant positive improvements were higher in pain and impact of disability (67.93%, P=.049) and participation and physical health (60.00%, P=.042).ConclusionCBFAE training contributes majorly to improved standing, walking, jumping and running and self-esteem, quality of life of children with spastic CP. Clinicians and exercise therapists should essentially incorporate CBFAE training and activities into the management of children with CP for improved mobility and functional performances.     

Indication of Risk of Mother-to-Child <Emphasis Type="Italic">Toxoplasma gondii</Emphasis> Transmission in the Greater Accra Region of Ghana

Objectives Congenital infection with Toxoplasma gondii is known to result in neurological and brain disorders including ophthalmic disorders later in life. Research in Ghana revealed high sero-prevalence among pregnant women and eye patients. This study determines the risk of congenital transmission of T. gondii infection in Accra, Ghana. Methods One hundred consented pregnant women aged 18–45 years (mean 29.85 ± 5.76) participated. Venous blood and tissue samples were taken from the maternal side of each placenta after delivery. Cord blood samples were also taken after they were separated from the infants. Finger-prick blood was taken from infants of participating women at 2 or 6 weeks post-natal. ELISA was used to detect T. gondii antibodies in all blood samples while Nested-PCR was used to detect T. gondii DNA from placental tissues. Data was analysed using SPSS v. 16. Results Overall, 37.6 % of maternal blood, 39.5 % of umbilical cord blood, and 57.5 % of post-natal infant blood were positive for anti-T. gondii IgG. No anti-T. gondii IgM was detected in any of those samples. Toxoplasma gondii DNA was detected in 39.8 % of placental tissue samples. Strong association was observed in the occurrence of placental T. gondii DNA and anti-T. gondii IgG positive women (ø = 0.810, p < 0.00001) as well as high Relative risk shown in the likelihood of foetal exposure to infection in latently-infected women (RR 10.39; CI 4.47–24.17; p < 0.00001). Conclusions for Practice The presence of anti-T. gondii IgG antibodies only, and T. gondii DNA in placental tissues indicate the women might have been infected early during the pregnancy, placing about 39.8 % of the babies at risk. These results can strongly influence policy to screen and treat pregnant women for T. gondii infection.     

A Training Program for Pharmacy Students on Providing Diabetes Care

Objective. To compare second- and third-year pharmacy students’ competence, attitudes, and self-confidence in providing diabetes care before and after completing a hand-on diabetes training program and to determine if the program had an impact on students’ attitude and self-confidence based on their year in the curriculum.Design. The program included classroom lectures and hands-on learning sessions in 5 facets of diabetes care. Pre- and post-test instruments measured students’ competence, attitudes, and confidence in diabetes care.Assessment. Students’ competence and the mean overall confidence score significantly improved after completing the program, while mean overall attitude score did not. Third-year students had significantly higher confidence scores than did second-year students on both pre- and post-program tests. No significant difference was found for attitude scores between second- and third-year students.Conclusion. The hands-on learning program was an effective approach to training pharmacy students in diabetes care, improving both their competence and confidence.     

Effects of an ethanol extract and the diterpene,xylopic acid,of Xylopia aethiopica fruits in murine models of musculoskeletal pain

Context: Fruits of Xylopia aethiopica (Dunal) A. Rich. (Annonaceae) are used traditionally to manage arthritis, headache and other pain disorders.

Objective: The analgesic properties of the X. aethiopica ethanol fruit extract (XAE) and xylopic acid (XA) were evaluated in musculoskeletal pain models.

Materials and methods: Acute muscle pain was induced in gastrocnemius muscle of Sprague–Dawley rats with 3% carrageenan (i.m.). Rats received XAE (30–300?mg/kg), XA (10–100?mg/kg) or morphine (1–10?mg/kg) after 12?h. Effects of XAE and XA on muscle pain were assessed by measuring post-treatment grip strength of the rats. Chronic muscle pain was similarly induced, but drug treatment was on the eighth day and effects of XAE and XA assessed with Randall–Selitto test for hyperlagesia. Acute-skeletal pain was induced in knee joints of rats with 3% carrageenan-kaolin mixture and effects determined 12-h later. Similar induction protocol was used for chronic knee pain with treatment and measurement as done for chronic muscle pain.

Results: XAE and XA significantly and dose-dependently ameliorated both acute muscle (ED₅₀ mg/kg: XAE?=?22.9; XA?=?6.2) and skeletal hyperalgesia (XAE?=?39.9; XA?=?17.7) induced by 3% carrageenan. Similarly, chronic skeletal hyperalgesia was reduced by XAE and XA treatment similar to morphine (ED₅₀: XAE?=?13.0; XA?=?4.6). This reduction was also seen in chronic muscle hyperalgesia (ED₅₀: XAE?=?79.1; XA?=?42.7). XAE and XA significantly reduced the spread of hyperalgesia to contralateral limbs in both models of chronic hyperalgesia.

Conclusion: These findings establish analgesic properties of the ethanol fruit extract of X. aethiopica and xylopic acid in musculoskeletal pain.     

Challenges in linking health research to policy: a commentary on developing a multi-stakeholder response to orphans and vulnerable children in Ghana

The Research and Development Division (RDD) of the Ghana Health Service (GHS) has a remit to build research capacity and conduct policy relevant research. By being situated within the GHS, RDD has good access to directors and programme managers, within and beyond the Ministry of Health. This structure has been facilitating collaboration through research cycles for 20 years, from agenda setting to discussions on policy relevance.This approach has been applied to research activities within the Addressing the Balance of Burden in AIDS (ABBA) Research Programme Consortium to tackle the challenges facing HIV affected orphans and vulnerable children (OVCs). The government strategy on OVCs recommends they should be encouraged to live in their home communities rather than in institutions. We present lessons here on efforts to use research to build a response across different agencies to address the problems that communities and families face in caring for these children in their communities.This approach to building consensus on research priorities points to the value of collaboration and dialogue with multiple stakeholders as a means of fostering ownership of a research process and supporting the relevance of research to different groups. Our experience has shown that if the context within which researchers, policy makers and stakeholders work were better understood, the links between them were improved and research were communicated more effectively, then better policy making which links across different sectors may follow. At the same time, collaboration among these different stakeholders to ensure that research meets social needs, must also satisfy the requirements of scientific rigour.     

Immunogenicity of novel nanoparticle-coated MSP-1 C-terminus malaria DNA vaccine using different routes of administration

An important aspect in optimizing DNA vaccination is antigen delivery to the site of action. In this way, any alternative delivery system having higher transfection efficiency and eventual superior antibody production needs to be further explored. The novel nanoparticle, pDNA/PEI/γ-PGA complex, is one of a promising delivery system, which is taken up by cells and is shown to have high transfection efficiency. The immunostimulatory effect of this novel nanoparticle (NP) coated plasmid encoding Plasmodium yoelii MSP1-C-terminus was examined. Groups of C57BL/6 mice were immunized either with NP-coated MSP-1 plasmid, naked plasmid or NP-coated blank plasmid, by three different routes of administration; intravenous (i.v.), intraperitoneal (i.p.) and subcutaneous (s.c). Mice were primed and boosted twice at 3-week intervals, then challenged 2 weeks after; and 100%, 100% and 50% mean of survival was observed in immunized mice with coated DNA vaccine by i.p., i.v. and s.c., respectively. Coated DNA vaccine showed significant immunogenicity and elicited protective levels of antigen specific IgG and its subclass antibody, an increased proportion of CD4⁺ and CD8⁺ T cells and INF-γ and IL-12 levels in the serum and cultured splenocyte supernatant, as well as INF-γ producing cells in the spleen. We demonstrate that, NP-coated MSP-1 DNA-based vaccine confers protection against lethal P. yoelii challenge in murine model across the various route of administration and may therefore, be considered a promising delivery system for vaccination.     

Cockroaches (Periplaneta americana) as carriers of agents of bacterial diarrhoea in Accra, Ghana

Bodies and intestinal contents of 208 cockroaches (Periplaneta americana), collected from kitchens in Accra and some surrounding villages were cultured for enteric bacterial pathogens. Six of them harboured three different serogroups of Salmonella, one had Shigella dysenteriae, 64 had Coliforms, 13 had Proteus species, two had Pseudomonas species and the rest (122) carried none of the bacterial species mentioned above. The presence of Salmonella species Shigella dysenteriae and Coliforms in these insects, which were collected from kitchens where foods are kept, points to the facts that these insects could play an important role in the transmission of these pathogenic organisms, especially in our environment. Permanent solution to these bacterial diarrhoea disease problems could only be solved when food, animals and the environments are free of these microbes.