Risk factors for HIV-1 infection in a longitudinal, prospective cohort of adults from the Mbeya Region, Tanzania

Steffen Geis, MD,1,2,* Leonard Maboko, MD, PhD,2,* Elmar Saathoff, PhD,1 Oliver Hoffmann, MD, PhD,1,2 Christof Geldmacher, PhD,1,2 Donan Mmbando, MD,3 Eleuter Samky, MD,4 Nelson L. Michael, MD, PhD,5,6 Deborah L. Birx, MD,7 Merlin L. Robb, MD,5,8 and Michael Hoelscher, MD, PhD1,2

To control the global HIV epidemic targeted interventions to reduce the incidence of HIV infections are urgently needed until an effective HIV vaccine is available. This study describes HIV-1 incidence and associated risk factors in a general population cohort of adults from Mbeya Region, Tanzania, who participated in a vaccine preparedness study.

Published at:  2011-04-15

Preferential infection and depletion of Mycobacterium tuberculosis–specific CD4 T cells after HIV-1 infection

Christof Geldmacher, Njabulo Ngwenyama, Alexandra Schuetz, Constantinos Petrovas, Klaus Reither, Edwin J. Heeregrave, Joseph P. Casazza, David R. Ambrozak, Mark Louder, William Ampofo, Georgios Pollakis, Brenna Hill, Erica Sanga, Elmar Saathoff, Leonard Maboko, Mario Roederer, William A. Paxton, Michael Hoelscher, Richard A. Koup

HIV-1 infection results in the progressive loss of CD4 T cells. In this study, we address how different pathogen-specific CD4 T cells are affected by HIV infection and the cellular parameters involved. We found striking differences in the depletion rates between CD4 T cells to two common opportunistic pathogens, cytomegalovirus (CMV) and Mycobacterium tuberculosis (MTB). CMV-specific CD4 T cells persisted after HIV infection, whereas MTB-specific CD4 T cells were depleted rapidly. CMV-specific CD4 T cells expressed a mature phenotype and produced very little IL-2, but large amounts of MIP-1β. In contrast, MTB-specific CD4 T cells were less mature, and most produced IL-2 but not MIP-1β. Staphylococcal enterotoxin B–stimulated IL-2–producing cells were more susceptible to HIV..........

Published at:  2010-11-29

Class I HLA-A*7401 Is Associated with Protection from HIV-1 Acquisition and Disease Progression in Mbeya, Tanzania

Rebecca N. Koehler, Anne M. Walsh, Elmar Saathoff, Sodsai Tovanabutra, Miguel A. Arroyo, Jeffrey R. Currier, Leonard Maboko, Michael Hoelsher, Merlin L. Robb, Nelson L. Michael, Francine E. McCutchan, Jerome H. Kim, Gustavo H. Kijak

Here we explore associations between HLA variation and human immunodeficiency virus type 1 (HIV-1) acquisition and disease progression in a community cohort in Mbeya, Tanzania, a region that, despite harboring high rates of HIV- 1 infection, remains understudied. African-specific allele HLA-A*74:01 was associated with decreased risk of infection (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.14–0.80; P = .011) and with protection from ..........

Published at:  2010-11-15

Electronic-Nose Technology Using Sputum Samples in Diagnosis of Patients with Tuberculosis

Authors: Arend Kolk, Michael Hoelscher, Leonard Maboko, Jutta Jung, Sjoukje Kuijper, Michael Cauchi, Conrad Bessant, Stella van Beers, Ritaban Dutta, Tim Gibson, Klaus Reither

We investigated the potential of two different electronic noses (EN; code named “Rob” and “Walter”) to differentiate between sputum headspace samples from tuberculosis (TB) patients and non-TB patients. Only samples from Ziehl-Neelsen stain (ZN)- and Mycobacterium tuberculosis culture-positive (TBPOS) sputum samples and ZN- and culture-negative (TBNEG) samples were used for headspace.......

Published at:  2010-11-01

Viral and host factors associated with the HIV-1 viral load setpoint in adults from Mbeya Region, Tanzania

Elmar Saathoff, PhD,a,* Michael Pritsch, MD,a,* Christof Geldmacher, PhD,a Rebecca N. Koehler, PhD,b,c Leonard Maboko, MD, PhD,d Lucas Maganga, MD,d Steffen Geis, MD, PhD,a,d Francine E. McCutchan, PhD,b,c Gustavo H. Kijak, PhD,b,c Jerome H. Kim, MD,b,e Miguel A. Arroyo, PhD,b,f Martina Gerhardt, PhD,a,d Sodsai Tovanabutra, PhD,b,c Merlin L. Robb, MD,b,c Carolyn Williamson, PhD,g Nelson L. Michael, MD, PhD,b,e and Michael Hoelscher, MD, PhDa

The viral load setpoint (VLS) is an important predictor of HIV disease progression, but there is a lack of information regarding the VLS and its possible determinants in African populations.

Published at:  2010-07-01

A Phase 1/2 Study of a Multiclade HIV-1 DNA Plasmid Prime and Recombinant Adenovirus Serotype 5 Boost Vaccine in HIV-Uninfected East Africans (RV 172)

Hannah Kibuuka, Robert Kimutai, Leonard Maboko, Fred Sawe, Mirjam S. Schunk, Arne Kroidl, Douglas Shaffer, Leigh Anne Eller, Rukia Kibaya, Michael A. Eller, Karin B. Schindler, Alexandra Schuetz, Monica Millard, Jason Kroll, Len Dally, Michael Hoelscher, Robert Bailer, Josephine H. Cox, Mary Marovich, Deborah L. Birx, Barney Graham, Nelson L. Michael, Mark S. de Souza, Merlin L. Robb

Human immunodeficiency virus (HIV) vaccine development remains a global priority. We describe the safety and immunogenicity of a multiclade DNA vaccine prime with a replication-defective recombinant adenovirus serotype 5 (rAd5) boost......

Published at:  2010-02-15

Implications of Storing Urinary DNA from Different Populations for Molecular Analyses

Angela Cannas ,Glendah Kalunga ,Clare Green ,Ludovica Calvo,Patrick Katemangwe,Klaus Reither,Mark D. Perkins,Leonard Maboko,Michael Hoelscher,Elizabeth A. Talbot,Peter Mwaba,Alimuddin I. Zumla,Enrico Girardi,Jim F. Huggett,for the TB trDNA consortium

Molecular diagnosis using urine is established for many sexually transmitted diseases and is increasingly used to diagnose tumours and other infectious diseases. Storage of urine prior to analysis, whether due to home collection or bio-banking, is increasingly advocated yet no best practice has emerged. Here, we examined the stability of DNA in stored urine in two populations over 28 days.

Published at:  2009-09-10

Low sensitivity of a urine LAM-ELISA in the diagnosis of pulmonary tuberculosis

Klaus Reither, Elmar Saathoff, Jutta Jung, Lilian T Minja, Inge Kroidl, Eiman Saad, Jim F Huggett, Elias N Ntinginya, Lucas Maganga, Leonard Maboko & Michael Hoelscher

The development and evaluation of rapid and accurate new diagnostic tools is essential to improve tuberculosis (TB) control in developing countries. In a previous study, the first release of a urine LAM-ELISA by Chemogen (Portland, USA) has been evaluated with a promising sensitivity and specificity for the diagnosis of pulmonary TB. In the present study, the now commercially available assay has been clinically assessed regarding its diagnostic value alone and in combination with clinical co-factors

Published at:  2009-08-28

Minor viral and host genetic polymorphisms can dramatically impact the biologic outcome of an epitope-specific CD8 T-cell response

Christof Geldmacher, Ian S. Metzler, Sodsai Tovanabutra, Tedi E. Asher, Emma Gostick, David R. Ambrozak, Constantinos Petrovas, Alexandra Schuetz, Njabulo Ngwenyama, Gustavo Kijak, Leonard Maboko, Michael Hoelscher, Francine McCutchan, David A. Price, Daniel C. Douek, Richard A. Koup

Human immunodeficiency virus-1 subtypes A and C differ in the highly conserved Gag-TL9 epitope at a single amino acid position. Similarly, the TL9 presenting human leukocyte antigen (HLA) class I molecules B42 and B81 differ only at 6 amino acid positions. Here, we addressed the influence of such minor viral and host genetic variation on the TL9-specific CD8 T-cell response. The clonotypic characteristics of CD8 T-cell populations elicited by subtype A or subtype C were distinct, and these responses differed substantially with respect to the recognition and selection of TL9 variants. Irrespective of the presenting.......

Published at:  2009-08-20

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