Improving validity of informed consent for biomedical research in Zambia using a laboratory exposure intervention.

BACKGROUND: Complex biomedical research can lead to disquiet in communities with limited exposure to scientific discussions, leading to rumours or to high drop-out rates. We set out to test an intervention designed to address apprehensions commonly encountered in a community where literacy is uncommon, and where complex biomedical research has been conducted for over a decade. We aimed to determine if it could improve the validity of consent. METHODS: Data were collected using focus group discussions, key informant interviews and observations. We designed an intervention that exposed participants to a detailed demonstration of laboratory processes. Each group was interviewed twice in a day, before and after exposure to the intervention in order to assess changes in their views. RESULTS: Factors that motivated people to participate in invasive biomedical research included a desire to stay healthy because of the screening during the recruitment process, regular advice from doctors, free medical services, and trust in the researchers. Inhibiting factors were limited knowledge about samples taken from their bodies during endoscopic procedures, the impact of endoscopy on the function of internal organs, and concerns about the use of biomedical samples. The belief that blood can be used for Satanic practices also created insecurities about drawing of blood samples. Further inhibiting factors included a fear of being labelled as HIV positive if known to consult heath workers repeatedly, and gender inequality. Concerns about the use and storage of blood and tissue samples were overcome by a laboratory exposure intervention. CONCLUSION: Selecting a group of members from target community and engaging them in a laboratory exposure intervention could be a useful tool for enhancing specific aspects of consent for biomedical research. Further work is needed to determine the extent to which improved understanding permeates beyond the immediate group participating in the intervention

No evidence for association with APOL1 kidney disease risk alleles and Human African Trypanosomiasis in two Ugandan populations:

Human African trypanosomiasis (HAT) manifests as an acute form caused by Trypanosoma brucei rhodesiense (Tbr) and a chronic form caused by Trypanosoma brucei gambiense (Tbg). Previous studies have suggested a host genetic role in infection outcomes, particularly for APOL1. We have undertaken a candidate gene association studies (CGAS) in a Ugandan Tbr and a Tbg HAT endemic area, to determine whether polymorphisms in IL10, IL8, IL4, HLAG, TNFA, TNX4LB, IL6, IFNG, MIF, APOL1, HLAA, IL1B, IL4R, IL12B, IL12R, HP, HPR, and CFH have a role in HAT

Photo-affinity labelling and biochemical analyses identify the target of trypanocidal simplified natural product analogues

This work was supported by the Leverhulme Trust (Grant number RL2012-025). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Current drugs to treat African sleeping sickness are inadequate and new therapies are urgently required. As part of a medicinal chemistry programme based upon the simplification of acetogenin-type ether scaffolds, we previously reported the promising trypanocidal activity of compound 1 , a bis-tetrahydropyran 1,4-triazole (B-THP-T) inhibitor. This study aims to identify the protein target(s) of this class of compound in Trypanosoma brucei to understand its mode of action and aid further structural optimisation. We used compound 3 , a diazirine- and alkyne-containing bi-functional photo-affinity probe analogue of our lead B-THP-T, compound 1 , to identify potential targets of our lead compound in the procyclic form T. brucei. Bi-functional compound 3 was UV cross-linked to its target(s) in vivo and biotin affinity or Cy5.5 reporter tags were subsequently appended by Cu(II)-catalysed azide-alkyne cycloaddition. The biotinylated protein adducts were isolated with streptavidin affinity beads and subsequent LC-MSMS identified the FoF1-ATP synthase (mitochondrial complex V) as a potential target. This target identification was confirmed using various different approaches. We show that (i) compound 1 decreases cellular ATP levels (ii) by inhibiting oxidative phosphorylation (iii) at the FoF1-ATP synthase. Furthermore, the use of GFP-PTP-tagged subunits of the FoF1-ATP synthase, shows that our compounds bind specifically to both the α- and β-subunits of the ATP synthase. The FoF1-ATP synthase is a target of our simplified acetogenin-type analogues. This mitochondrial complex is essential in both procyclic and bloodstream forms of T. brucei and its identification as our target will enable further inhibitor optimisation towards future drug discovery. Furthermore, the photo-affinity labeling technique described here can be readily applied to other drugs of unknown targets to identify their modes of action and facilitate more broadly therapeutic drug design in any pathogen or disease model.Publisher PDFPeer reviewe

An overview of DNA fingerprinting

No Abstract Available Journal of Science and Technology Vol.1(2) 1997: 29-35 Published 200

Caractérisation tectono-métamorphique de la zone de cisaillement ductile de Mugesse, Ubendian Belt (Malawi)

International audienc

Caractérisation tectono-métamorphique de la zone de cisaillement ductile de Mugesse, Ubendian Belt (Malawi)

International audienc

Tectono-metamorphic evolution and strain partitioning along the Mugesse mega shear zone, Ubendian Belt (Northern Malawi)

International audienceIn this contribution we focus on a portion of the Mugesse mega shear zone (MGSZ) in the Ubendian Belt, for which details on kinematics and strain partitioning remains poorly documented. We present a field-based structural work, a petrological and thermobarometrical study of mylonites and LA-ICP-MS in-situ U-Pb dating on monazite and zircon. The detailed field mapping highlights that the whole study area shows the same sinistral strain pattern with deformation being partitioned within S-C and C-C’ structures. Syn-kinematic metamorphic mineral assemblages indicate that the MGSZ mylonites recorded a clockwise P-T evolution with peak temperature conditions at upper amphibolite metamorphic facies of 11–15 kbar and 760–790 °C. Retrogression and cooling reached P-T conditions of 1–7 kbar and 330–480 °C. LA-ICP-MS in-situ U-Pb monazite dating suggests that the main activity of the MGSZ was Pan-African, at ca. 547 ± 5 and 545 ± 4 Ma. Zircon dates at 1985 ± 44 Ma and 1127 ± 29–988 ± 10 Ma are interpreted as inherited ages of potentially detrital origin related to the Ubendian and Irumide orogeny, respectively. A 1146 ± 14 Ma date obtained on zircons from the Lwakwa mylonitic orthogneiss is interpreted as the crystallisation age of the granitic protolith that intruded the Paleoproterozoic basement. Strain partitioning and strain softening during the growth of the MGSZ was strongly controlled by feedback relationships between deformation and retrograde metamorphism enhanced by fluid ingress and recrystallisation

Tuberculin sensitivity and HIV-1 status of patients attending a sexually transmitted diseases clinic in Lusaka, Zambia: a cross-sectional study.

A cross-sectional study to estimate the prevalence of latent tuberculosis (TB) in a group of Zambians at high risk of human immunodeficiency virus type 1 (HIV-1) infection and to examine the effect of HIV-1 infection on the tuberculin response was conducted in the University Teaching Hospital in Lusaka, Zambia during July to September 1990. Patients were selected from those presenting to the out-patient clinic for first referral with either sexually transmitted or skin disease. 268 adults were included in the study; 158 (59%; 95% confidence interval [CI] = 53-65%) were HIV-1 antibody positive. Of 82 HIV-1 negative participants who returned for Mantoux skin test reading, 51 (62%; 95% CI = 57-67%) had a positive test reaction (diameter > or = 10 mm) after receiving 2 units of RT-23 tuberculin. Of 106 HIV-1 positive participants who returned, only 32 (30%; 95% CI = 26-34%) had a diameter > or = 10 mm. Nine (28%) of the HIV-1 positive and Mantoux positive participants had large reactions > or = 30 mm, compared to 4 (8%) of the HIV-1 negative, Mantoux positive participants (P = 0.03). Results in the HIV-1 negative group indicated a prevalence of latent TB of 62% in this population. HIV-1 infection was associated with a much higher frequency of negative response to tuberculin and with a few large skin test responses. Thus, in populations where HIV seropositivity is high, Mantoux skin tests cannot be used to assess those with latent TB who might benefit from chemoprophylaxis

Impact assessment risk management tools

FARMAF polcy briefIn this policy paper we provide more insight into the impact assessment framework and address related policy issues. First, we elaborate on the current state of affairs of three risk management tools analysed within the FARMAF project, namely insurance in Zambia and Burkina Faso, warehouse receipt systems in Tanzania and Burkina Faso, and market information systems in all three countries. Subsequently, methodological approaches fostering lesson-sharing, challenges encountered and related policy issues are discussed