Mycobacterium tuberculosis proteins involved in cell wall lipid biosynthesis improve BCG vaccine efficacy in a murine TB model

OBJECTIVES: Advances in tuberculosis (TB) vaccine development are urgently required to enhance global disease management. We evaluated the potential of Mycobacterium tuberculosis (M. tb)-derived protein antigens Rv0447c, Rv2957 and Rv2958c to boost BCG vaccine efficacy in the presence or absence of glucopyranosyl lipid adjuvant formulated in a stable emulsion (GLA-SE) adjuvant. METHODS: Mice received the BCG vaccine, followed by Rv0447c, Rv2957 and Rv2958c protein boosting with or without GLA-SE adjuvant 3 and 6 weeks later. Immune responses were examined at given time points. 9 weeks post vaccination, mice were aerosol-challenged with M. tb, and sacrificed at 6 and 12 weeks to assess bacterial burden. RESULTS: Vaccination of mice with BCG and M. tb proteins in the presence of GLA-SE adjuvant triggered strong IFN-γ and IL-2 production by splenocytes; more TNF-α was produced without GLA-SE addition. Antibody responses to all three antigens did not differ, with or without GLA-SE adjuvant. Protein boosting without GLA-SE adjuvant resulted in vaccinated animals having better control of pulmonary M. tb load at 6 and 12 weeks post aerosol infection, while animals receiving the protein boost with GLA-SE adjuvant exhibited more bacteria in the lungs. CONCLUSIONS: Our data provides evidence for developing Rv2958c, Rv2957 and Rv0447c in a heterologous prime-boost vaccination strategy with BCG

Inkjet-printed graphene electrodes for dye-sensitized solar cells

We present a stable inkjet printable graphene ink, formulated in isopropyl alcohol via liquid phase exfoliation of chemically pristine graphite with a polymer stabilizer. The rheology and low deposition temperature of the ink allow uniform printing. We use the graphene ink to fabricate counter electrodes (CE) for natural and ruthenium-based dye-sensitized solar cells (DSSCs). The repeatability of the printing process for the CEs is demonstrated through an array of inkjet-printed graphene electrodes, with ∼5% standard deviation in the sheet resistance. As photosensitizers, we investigate natural tropical dye extracts from Pennisetum glaucum, Hibiscus sabdariffa and Caesalpinia pulcherrima. Among the three natural dyes, we find extracts from C. pulcherrima exhibit the best performance, with ∼0.9% conversion efficiency using a printed graphene CE and a comparable ∼1.1% efficiency using a platinum (Pt) CE. When used with N719 dye, the inkjet-printed graphene CE shows a ∼3.0% conversion efficiency, compared to ∼4.4% obtained using Pt CEs. Our results show that inkjet printable graphene inks, without any chemical functionalization, offers a flexible and scalable fabrication route, with a material cost of only ∼2.7% of the equivalent solution processed Pt-based electrodes.Authors acknowledge support from CAPREX, Cambridge Africa Alborada Fund, Carnegie-University of Ghana Next Generation of Africa Academics programme and the Royal Academy of Engineering (RAEng) through a research fellowship (Graphlex)

Correct Dosing of Artemether-Lumefantrine for Management of Uncomplicated Malaria in Rural Tanzania: Do facility and Patient Characteristics Matter?

Use of artemisinin-based combination therapy (ACT), such as artemether-lumefantrine (AL), requires a strict dosing schedule that follows the drugs' pharmacokinetic properties. The quality of malaria case management was assessed in two areas in rural Tanzania, to ascertain patient characteristics and facility-specific factors that influence correct dosing of AL for management of uncomplicated malaria. Exit interviews were conducted with patients attending health facilities for initial illness consultation. Information about health workers' training and supervision visits was collected. Health facilities were inventoried for capacity and availability of medical products related to care of malaria patients. The outcome was correct dosing of AL based on age and weight. Logistic regression was used to assess health facility factors and patient characteristics associated with correct dosing of AL by age and weight. A total of 1,531 patients were interviewed, but 60 pregnant women were excluded from the analysis. Only 503 (34.2%) patients who received AL were assessed for correct dosing. Most patients who received AL (85.3%) were seen in public health facilities, 75.7% in a dispensary and 91.1% in a facility that had AL in stock on the survey day. Overall, 92.1% (463) of AL prescriptions were correct by age or weight; but 85.7% of patients received correct dosing by weight alone and 78.5% received correct dosing by age alone. In multivariate analysis, patients in the middle dosing bands in terms of age or weight, had statistically significant lower odds of correct AL dosing (p < 0.05) compared to those in the lowest age or weight group. Other factors such as health worker supervision and training on ACT did not improve the odds of correct AL dosing. Although malaria treatment guidelines indicate AL dosing can be prescribed based on age or weight of the patient, findings from this study show that patients within the middle age and weight dosing bands were least likely to receive a correct dose by either measure. Clinicians should be made aware of AL dosing errors for patients aged three to 12 years and advised to use weight-based prescriptions whenever possible

Predictors of Antibiotics Co-prescription with Antimalarials for Patients Presenting with Fever in Rural Tanzania.

Successful implementation of malaria treatment policy depends on the prescription practices for patients with malaria. This paper describes prescription patterns and assesses factors associated with co-prescription of antibiotics and artemether-lumefantrine (AL) for patients presenting with fever in rural Tanzania. From June 2009 to September 2011, a cohort event monitoring program was conducted among all patients treated at 8 selected health facilities in Ifakara and Rufiji Health and Demographic Surveillance System (HDSS).It included all patients presenting with fever and prescribed with AL. Logistic regression was used to model the predictors on the outcome variable which is co-prescription of AL and antibiotics on a single clinical visit. A cohort of 11,648 was recruited and followed up with 92% presenting with fever. Presumptive treatment was used in 56% of patients treated with AL. On average 2.4 (1 -- 7) drugs was prescribed per encounter, indicating co-prescription of AL with other drugs. Children under five had higher odds of AL and antibiotics co-prescription (OR = 0.63, 95% CI: 0.46 -- 0.85) than those aged more than five years. Patients testing negative had higher odds (OR = 2.22, 95%CI: 1.65 -- 2.97) of AL and antibiotics co-prescription. Patients receiving treatment from dispensaries had higher odds (OR = 1.45, 95% CI: 0.84 -- 2.30) of AL and antibiotics co-prescription than those from served in health centres even though the deference was not statistically significant. Regardless the fact that Malaria is declining but due to lack of laboratories and mRDT in most health facilities in the rural areas, clinicians are still treating malaria presumptively. This leads them to prescribe more drugs to treat all possibilities

The Hydrochemistry of Groundwater in Some Communities in the Ayensu River Basin in the Central Region of Ghana

Hydrochemical analysis of groundwater samples in some communities in the Ayensu river basin of the central Region of Ghana was used to establish the hydrochemistry of the study area. The methodology consisted of physicochemical sampling and laboratory analysis of groundwater resources in the Basin and basic statistical analysis of the laboratory results. Generally, the groundwater is weakly acidic with a mean pH value of 6.32, had high electrical conductivity and TDS values in the range, 256.4 µS cm-1 to 2313.3 µS cm-1 and 101.7 mg/L to 1247.0 mg/L respectively. The groundwater in the area is undersaturated with respect to carbonate phases and is fresh except for one borehole at Gyangyanadze which has TDS value of 1247.0 mg/L considered as saline water.  The dominant water types in the study area are Na- Cl, Ca- Mg - Cl and Ca - Mg - SO4. The groundwater is to a large extent potable. However, approximately 13% of the groundwater samples had chloride concentrations slightly exceeding the respective WHO maximum acceptable limits for drinking water. Approximately 43%, 16% and 10% respectively of the water samples had Al3+, Fe2+ and Cd2+ concentrations above the respective WHO maximum acceptable limit for drinking water.  Silicate mineral weathering is probably the main process through which major ions enter the groundwater. Keywords:Groundwater quality  hydrochemistry  silicate weathering  Central Region  Ghana 

Pharmacogenetics in Ghana: Reviewing the evidence

Different clinical response of different patients to the same medicine has been recognised and documented since the 1950’s. Variability in response of individuals to standard doses of drug therapy is important in clinicalpractice and can lead to therapeutic failures or adverse drug reactions. Pharmacogenetics seeks to identify individual genetic differences (polymorphisms) in drug absorption, metabolism, distribution and excretion that can affect the activity of a particular drug with theview of improving efficacy and reducing toxicity. Although knowledge of pharmacogenetics is being translated into clinical practice in the developed world, its applicability in the developing countries is low. Severalfactors account for this including the fact that there is very little pharmacogenetic information available in many indigenous African populations including Ghanaians. A number of genes including Cytochrome P450 (CYP) 2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, MDR1 and TPMT have been genotyped in the Ghanaian population since the completion of the Human genome project. There is however, an urgentneed to increase pharmacogenetic research in Ghana to increase availability of data. Introducing Pharmacogenetics into the curriculum of Medical and Pharmacy training institutions will influence translatingknowledge of pharmacogenetics into clinical practice. This will also equip health professionals with the skill to integrate genetic information into public health decision making

Adverse drug reaction reporting by doctors in a developing country: A case study from Ghana

Background: Spontaneous adverse drug reaction reporting is the most widely used and cost effective method of monitoring the safety of drugs. This method is heavily afflicted by underreporting by healthcare professionals. The study aims at assessing adverse drug reaction (ADR) reporting rate by doctors, knowledge of the reporting system and attitudes to SADR in the Greater Accra region.Methods: This was a cross sectional survey of 259 doctors randomly  selected from 23 hospitals classified as government 199 (76.8%), quasi-governmental 43(16.6%) and private 17 (6.6%) hospitals in the Greater Accra Region of Ghana. Data collection was by self-administered  questionnaire from May 5, 2012- July 6, 2012. Descriptive statistics was used to describe the background characteristics of the doctors and the outcome measures like training and reasons for ADR reporting were summarized as frequencies and percentages.Results: One-third (27.4%) of doctors surveyed had received previous training on drug safety monitoring and ADR reporting; training and  knowledge of the reporting system was found to improve reporting. Morethan half 154 (59.5%) of the doctors had seen a patient with suspected ADR in the past one year although only 31 (20%) had reported it by completing the SADR reporting form. Doctors working in government hospitals were about 5 times more likely to report than those in private hospitals [OR=4.94, 95%CI (1.55-15.69)].Conclusion: Training and knowledge of the ADR reporting system were found to be associated with the likelihood of reporting an ADR. Most of the doctors had not previously received training on ADR reporting.Keywords: Spontaneous reporting, adverse drug reaction, underreporting, doctors, Ghan

Analysis of photographic records of coal pyrolysis. Final report

Bituminous coals upon heating undergo melting and pyrolytic decomposition with significant parts of the coal forming an unstable liquid that can escape from the coal by evaporation. The transient liquid within the pyrolyzing coal causes softening or plastic behavior that can influence the chemistry and physics of the process. Bubbles of volatiles can swell the softened coal mass in turn affecting the combustion behavior of the coal particles. The swelling behavior of individual coal particles has to be taken into account both as the layout as well as for the operation of pyrolysis, coking and performance of coal-fired boilers. Increased heating rates generally increase the amount of swelling although it is also known that in some cases, even highly swelling coals can be transformed into char with no swelling if they are heated slowly enough. The swelling characteristics of individual coal particles have been investigated by a number of workers employing various heating systems ranging from drop tube and shock tube furnaces, flow rate reactors and electrical heating coils. Different methods have also been employed to determine the swelling factors. The following sections summarize some of the published literature on the subject and outline the direction in which the method of analysis will be further extended in the study of the swelling characteristics of hvA bituminous coal particles that have been pyrolyzed with a laser beam

A novel malaria vaccine candidate antigen expressed in Tetrahymena thermophila

Development of effective malaria vaccines is hampered by the problem of producing correctly folded Plasmodium proteins for use as vaccine components. We have investigated the use of a novel ciliate expression system, Tetrahymena thermophila, as a P. falciparum vaccine antigen platform. A synthetic vaccine antigen composed of N-terminal and C-terminal regions of merozoite surface protein-1 (MSP-1) was expressed in Tetrahymena thermophila. The recombinant antigen was secreted into the culture medium and purified by monoclonal antibody (mAb) affinity chromatography. The vaccine was immunogenic in MF1 mice, eliciting high antibody titers against both N- and C-terminal components. Sera from immunized animals reacted strongly with P. falciparum parasites from three antigenically different strains by immunofluorescence assays, confirming that the antibodies produced are able to recognize parasite antigens in their native form. Epitope mapping of serum reactivity with a peptide library derived from all three MSP-1 Block 2 serotypes confirmed that the MSP-1 Block 2 hybrid component of the vaccine had effectively targeted all three serotypes of this polymorphic region of MSP-1. This study has successfully demonstrated the use of Tetrahymena thermophila as a recombinant protein expression platform for the production of malaria vaccine antigens

Social sciences research in neglected tropical diseases 2: A bibliographic analysis

The official published version of the article can be found at the link below.Background There are strong arguments for social science and interdisciplinary research in the neglected tropical diseases. These diseases represent a rich and dynamic interplay between vector, host, and pathogen which occurs within social, physical and biological contexts. The overwhelming sense, however, is that neglected tropical diseases research is a biomedical endeavour largely excluding the social sciences. The purpose of this review is to provide a baseline for discussing the quantum and nature of the science that is being conducted, and the extent to which the social sciences are a part of that. Methods A bibliographic analysis was conducted of neglected tropical diseases related research papers published over the past 10 years in biomedical and social sciences. The analysis had textual and bibliometric facets, and focussed on chikungunya, dengue, visceral leishmaniasis, and onchocerciasis. Results There is substantial variation in the number of publications associated with each disease. The proportion of the research that is social science based appears remarkably consistent (<4%). A textual analysis, however, reveals a degree of misclassification by the abstracting service where a surprising proportion of the "social sciences" research was pure clinical research. Much of the social sciences research also tends to be "hand maiden" research focused on the implementation of biomedical solutions. Conclusion There is little evidence that scientists pay any attention to the complex social, cultural, biological, and environmental dynamic involved in human pathogenesis. There is little investigator driven social science and a poor presence of interdisciplinary science. The research needs more sophisticated funders and priority setters who are not beguiled by uncritical biomedical promises