Safety and Immunogenicity of PENNVAX-G DNA Prime Administered by Biojector 2000 or CELLECTRA Electroporation Device With Modified Vaccinia Ankara-CMDR Boost

Julie A Ake, Alexandra Schuetz, Poonam Pegu, Lindsay Wieczorek, Michael A Eller, Hannah Kibuuka, Fredrick Sawe, Leonard Maboko, Victoria Polonis, Nicos Karasavva, David Weiner, Arthur Sekiziyivu, Josphat Kosgei, Marco Missanga, Arne Kroidl, Philipp Mann, Silvia Ratto-Kim, Leigh Anne Eller, Patricia Earl, Bernard Moss, Julie Dorsey-Spitz, Mark Milazzo, G Laissa Ouedraogo, Farrukh Rizvi, Jian Yan, Amir S Khan, Sheila Peel, Niranjan Y Sardesai, Nelson L Michael, Viseth Ngauy, Mary Marovich, Merlin L Robb

We report the first-in-human safety and immunogenicity evaluation of PENNVAX-G DNA/modified vaccinia Ankara–Chiang Mai double recombinant (MVA-CMDR) prime-boost human immuonodeficiency virus (HIV) vaccine, with intramuscular DNA delivery by either Biojector 2000 needle-free injection system (Biojector) or CELLECTRA electroporation device.

Published at:  2017-11-01

Proceedings from the CIHLMU 5th Infectious Diseases Symposium 2016 “Drug Resistant Tuberculosis: Old Disease – New Challenge”

Authors: Celso Khosa, Krutarth Patel, Karlygash Abdiyeva, Nurkeldi Turebekov, Bettina Prüller & Norbert Heinrich

The 5th CIHLMU Infectious Disease Symposium, Munich, Germany, March 12, 2016 brought together Tuberculosis Experts from developed and low middle-income countries to discuss the control of drug resistance Tuberculosis. The meeting featured 9 presentations: Tuberculosis history and current scenario, Tuberculosis and migration - current scenario in Germany, Mechanism of Tuberculosis resistance development, Epidemiology of resistance – transmission vs. new generation of resistance, The impact of diagnostic in patients beyond – sensitivity and specificity, The Bangladesh regimen – new hope trough old drugs, New drugs and regimens – an overview on studies and Multi and Extensively Drug Resistant Tuberculosis from Europe. The presentations were followed by a panel discussion. Serious Multidrug Resistance epidemic in some countries may jeopardize the progress in Tuberculosis control. In this meeting epidemiology, mechanism, immigration and screening, diagnosis, research and treatment of drug resistant tuberculosis were discussed.

Published at:  2017-09-04

Persistence of Activated and Adaptive-Like NK Cells in HIV+ Individuals despite 2 Years of Suppressive Combination Antiretroviral Therapy

Authors: Anna C. Hearps1,2, imagePaul A. Agius3,4, imageJingling Zhou1, imageSamantha Brunt5, imageMkunde Chachage1, imageThomas A. Angelovich1, imagePaul U. Cameron6,7, imageMichelle Giles2,7, imagePatricia Price8, imageJulian Elliott2,7 and imageAnthony Jaworowski1,2*

Innate immune dysfunction persists in HIV+ individuals despite effective combination antiretroviral therapy (cART). We recently demonstrated that an adaptive-like CD56dim NK cell population lacking the signal transducing protein FcRγ is expanded in HIV+ individuals. Here, we analyzed a cohort of HIV+ men who have sex with men (MSM, n = 20) at baseline and following 6, 12, and 24 months of cART and compared them with uninfected MSM (n = 15) to investigate the impact of cART on NK cell dysfunction. Proportions of NK cells expressing markers of early (CD69+) and late (HLA-DR+/CD38+) activation were elevated in cART-naïve HIV+ MSM (p = 0.004 and 0.015, respectively), as were FcRγ− NK cells (p = 0.003). Using latent growth curve modeling, we show that cART did not reduce levels of FcRγ− NK cells (p = 0.115) or activated HLA-DR+/CD38+ NK cells (p = 0.129) but did reduce T cell and monocyte activation (p < 0.001 for all). Proportions of FcRγ− NK cells were not assoc..........

Published at:  2017-06-30

Linkage into care among newly diagnosed HIV-positive individuals tested through outreach and facility-based HIV testing models in Mbeya, Tanzania: a prospective mixed-method cohort study

Erica Samson Sanga1,2, Wondwossen Lerebo2,3, Adiel K Mushi4, Petra Clowes1,5, Willyhelmina Olomi1, Leonard Maboko1, Christina Zarowsky2,6

Linkage to care is the bridge between HIV testing and HIV treatment, care and support. In Tanzania, mobile testing aims to address historically low testing rates. Linkage to care was reported at 14% in 2009 and 28% in 2014. The study compares linkage to care of HIV-positive individuals tested at mobile/outreach versus public health facility-based services within the first 6 months of HIV diagnosis

Published at:  2017-04-12

Trichuris trichiura infection and its relation to environmental factors in Mbeya region, Tanzania: A cross-sectional, population-based study

Kirsi M. Manz ,Petra Clowes,Inge Kroidl,Dickens O. Kowuor,Christof Geldmacher,Nyanda E. Ntinginya,Leonard Maboko,Michael Hoelscher,Elmar Saathoff

The intestinal nematode Trichuris trichiura is among the most common causes of human infectious disease worldwide. As for other soil-transmitted nematodes, its reproductive success and thus prevalence and intensity of infection in a given area strongly depend on environmental conditions. Characterization of the influence of environmental factors can therefore aid to identify infection hot spots for targeted mass treatment.

Published at:  2017-04-06

HIV-1 Genetic Diversity Among Incident Infections in Mbeya, Tanzania

Erik Billings, Eric Sanders-Buell, Meera Bose, Gustavo H. Kijak, Andrea Bradfield, Jacqueline Crossler, Miguel A. Arroyo, Leonard Maboko, Oliver Hoffmann, Steffen Geis, Deborah L. Birx, Jerome H. Kim, Nelson L. Michael, Merlin L. Robb, Michael Hoelscher, and Sodsai Tovanabutra

In preparation for vaccine trials, HIV-1 genetic diversity was surveyed between 2002 and 2006 through the Cohort Development study in the form of a retrospective and prospective observational study in and around the town of Mbeya in Tanzania's Southwest Highlands. This study describes the molecular epidemiology of HIV-1 strains obtained from 97 out of 106 incident HIV-1 infections identified in three subpopulations of participants (one rural, two urban) from the Mbeya area. Near full-genome or half-genome sequencing showed a subtype distribution of 40% C, 17% A1, 1% D, and 42% inter-subtype recombinants. Compared to viral subtyping results previously obtained from the retrospective phase of this study, the overall proportion of incident viral strains did not change greatly during the study course, suggesting maturity of the epidemic. A comparison to a current Phase I-II vaccine being tested in Africa shows ∼17% amino acid sequence difference between the gp120 of the vaccine and subtype C incident strains. Phylogenetic and recombinant breakpoint analysis of the incident........

Published at:  2017-04-01

Why being an expert – despite xpert –remains crucial for children in high TB burden settings

Authors: Jason M. Bacha, Katherine Ngo, Petra Clowes, Heather R. Draper, Elias N. Ntinginya, Andrew DiNardo, Chacha Mangu, Issa Sabi, Bariki Mtafya & Anna M. Mandalakas

As access to Xpert expands in high TB-burden settings, its performance against clinically diagnosed TB as a reference standard provides important insight as the majority of childhood TB is bacteriologically unconfirmed. We aim to describe the characteristics and outcomes of children with presumptive TB and TB disease, and assess performance of Xpert under programmatic conditions against a clinical diagnosis of TB as a reference standard.

Published at:  2017-02-06

High-dose rifampicin, moxifloxacin, and SQ109 for treating tuberculosis: a multi-arm, multi-stage randomised controlled trial

Authors: Martin J Boeree PhD a †, Norbert Heinrich MD c d †, Rob Aarnoutse PhD b, Andreas H Diacon PhD e, Rodney Dawson PhD g, Sunita Rehal MSc o, Prof Gibson S Kibiki PhD h, Prof Gavin Churchyard FRCP q r t, Ian Sanne FRCP s, Nyanda E Ntinginya MD j, Lilian T Minja MD m, Robert D Hunt BSc n, Salome Charalambous PhD q, Madeleine Hanekom PhD e, Hadija H Semvua PhD h, Stellah G Mpagama PhD i, Christina Manyama MD j, Bariki Mtafya MSc j, Klaus Reither MD k l, Prof Robert S Wallis MD q…Prof Michael Hoelscher FRCP c d

Tuberculosis is now the leading infectious disease killer worldwide. Treatment regimens last at least 6 months, so shorter, safer, and more effective regimens for drug-sensitive tuberculosis are needed as part of the global strategy to eliminate the disease. .......

Published at:  2017-01-15

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