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New study on TB vaccine for newborns of HIV-positive mothers

New study on TB vaccine for newborns of HIV-positive mothers | IDM News | Scoop.it
University of Cape Town / Universiteit Kaapstad / iYunivesithi yaseKapa - the leading African university
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"UCT's South African Tuberculosis Vaccine Initiative (SATVI) and Stellenbosch's Desmond Tutu TB Centre have begun recruiting infants for a study to test a new TB vaccine, MVA85A, for newborns of HIV-positive moms. The MVA85A vaccine, developed by Oxford University, has already been successfully tested for safety in healthy adults, children, and in HIV positive adults. This will be the first new TB vaccine to be tested specifically for newborn babies of HIV-positive mothers."

 

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News and publications from the Institute of Infectious Disease and Molecular Medicine, University of Cape Town
Curated by Ed Rybicki
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Serial QuantiFERON testing and tuberculosis disease risk among young children: an observational cohort study

Serial QuantiFERON testing and tuberculosis disease risk among young children: an observational cohort study | IDM News | Scoop.it
In young children, tuberculosis disease risk was not significantly increased, and
QFT reversion was common, following QFT conversion at interferon-γ values up to 10
times the recommended test threshold (0·35 IU/mL). By contrast, QFT conversion at
very high interferon-γ values (>4·00 IU/mL) warrants intensified diagnostic and preventive
intervention because of the extremely high risk of tuberculosis disease in these young
children.
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Characterization of progressive HIV-associated tuberculosis using 2-deoxy-2-[18F]fluoro-D-glucose positron emission and computed tomography 

Characterization of progressive HIV-associated tuberculosis using 2-deoxy-2-[18F]fluoro-D-glucose positron emission and computed tomography  | IDM News | Scoop.it
Using combined positron emission and computed tomography (PET-CT), Esmail et al. show that some patients with latent tuberculosis have signs of subclinical, active disease in the lungs and a greater likelihood of progression, suggesting a spectrum of disease rather than discrete latent and active disease states.
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BIIIIIIG news out of SA - and the Institute!
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Norovirus at the RNC: Why This Virus Spreads So Quickly

Norovirus at the RNC: Why This Virus Spreads So Quickly | IDM News | Scoop.it
Norovirus has sickened several delegates from California at the Republican National Convention. Why is the virus so contagious?
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I could say it's because of the amount of shit getting spread around, if you take note of the location...?
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AIDS conference 2016: the gains, the gaps, the next global steps

AIDS conference 2016: the gains, the gaps, the next global steps | IDM News | Scoop.it
The focus of the 2016 International AIDS Conference has on access to necessary antiretrovirals, equity and making sure no-one is left behind. But there is a funding gap that needs to be addressed.
Ed Rybicki's insight:
Our very own Linda-Gail Bekker: now President of the organisation that holds these monster AIDS Conferences.
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What new GSK patent policy means for the developing world

Analysts welcome focus on cancer drugs for poorest countries but caution that more work needs to be done.
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Perfecting a viral pack mule: CPMV!

Perfecting a viral pack mule: CPMV! | IDM News | Scoop.it
LA JOLLA, CA - March 29, 2016 - Viruses aren't always bad. In fact, scientists can harness the capabilities of some viruses for good--modifying the viruses to carry drug molecules, for example.
..
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biovironanotech rules, OK?!
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CALL FOR PAPERS: Zika Virus Research

CALL FOR PAPERS: Zika Virus Research | IDM News | Scoop.it
The Zika Virus is the latest viral threat that is slowly spreading from country to country. The local transmission of Zika virus has been reported in more than 50 countries and the situation was declared as a public health emergency of international concern by the World Health Organization. As an open-access publisher, Frontiers believes that…
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Mathematicians mapped out every “Game of Thrones” relationship to find the main character

Mathematicians mapped out every “Game of Thrones” relationship to find the main character | IDM News | Scoop.it
Fans of the Game of Thrones books and TV series have long quarreled over who the true hero of the story is. Daenerys? Tyrion? Jon Snow? Hodor? Every time a character seems to be developing into a protagonist, he or she is brutally killed (video). Such is the perilous existence of the major players in the world of th
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Tyrion...Tyrion's going to win!!
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A blood RNA signature for tuberculosis disease risk: a prospective cohort study

Findings
Between July 6, 2005, and April 23, 2007, we enrolled 6363 participants from the ACS study and 4466 from independent South African and Gambian cohorts. 46 progressors and 107 matched controls were identified in the ACS cohort. A 16 gene signature of risk was identified. The signature predicted tuberculosis progression with a sensitivity of 66·1% (95% CI 63·2–68·9) and a specificity of 80·6% (79·2–82·0) in the 12 months preceding tuberculosis diagnosis. The risk signature was validated in an untouched group of adolescents (p=0·018 for RNA sequencing and p=0·0095 for qRT-PCR) and in the independent South African and Gambian cohorts (p values <0·0001 by qRT-PCR) with a sensitivity of 53·7% (42·6–64·3) and a specificity of 82·8% (76·7–86) in the 12 months preceding tuberculosis.

Interpretation
The whole blood tuberculosis risk signature prospectively identified people at risk of developing active tuberculosis, opening the possibility for targeted intervention to prevent the disease.
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SERIOUSLY powerful stuff out of UCT and the IDM!
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Prof Bongani Mayosi receives A rating

Prof Bongani Mayosi receives A rating | IDM News | Scoop.it
The National Research Foundation (NRF) has awarded Professor Bongani Mayosi, dean designate for the Faculty of Health Sciences, an A rating. This rating means he joins the ranks of leading international researchers in the view of the NRF.

The NRF uses its rating system to benchmark South African researchers against the rest of the world. Mayosi’s rating brings the number of A-rated researchers at UCT to 38.
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Medical Virology of Hepatitis B: how it began and where we are now?

Infection with hepatitis B virus (HBV) may lead to acute or chronic hepatitis. HBV infections were previously much more frequent but there are still 240 million chronic HBV carriers today and ca. 620,000 die per year from the late sequelae liver cirrhosis or hepatocellular carcinoma. Hepatitis B was recognized as a disease in ancient times, but its etiologic agent was only recently identified. The first clue in unraveling this mystery was the discovery of an enigmatic serum protein named Australia antigen 50 years ago by Baruch Blumberg. Some years later this was recognized to be the HBV surface antigen (HBsAg). Detection of HBsAg allowed for the first time screening of inapparently infected blood donors for a dangerous pathogen. The need to diagnose clinically silent HBV infections was a strong driving force in the development of modern virus diagnostics. HBsAg was the first infection marker to be assayed with a highly sensitive radio immune assay. HBV itself was among the first viruses to be detected by assay of its DNA genome and IgM antibodies against the HBV core antigen were the first to be selectively detected by the anti-μ capture assay. The cloning and sequencing of the HBV genome in 1978 paved the way to understand the viral life cycle, and allowed development of efficient vaccines and drugs. Today’s hepatitis B vaccine was the first vaccine produced by gene technology. Among the problems that still remain today are the inability to achieve a complete cure of chronic HBV infections, the recognition of occult HBV infections, their potential reactivation and the incomplete protection against escape mutants and heterologous HBV genotypes by HBV vaccines.
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TB Diagnosis in a Primary Care Clinic with High TB and HIV Prevalence in South Africa

TB Diagnosis in a Primary Care Clinic with High TB and HIV Prevalence in South Africa | IDM News | Scoop.it

Background

 

In 2012, about 8.6 million people developed active tuberculosis (TB)—a contagious mycobacterial disease that usually affects the lungs—and at least 1.3 million people died from the disease. Most of these deaths were in low- and middle-income countries, and a fifth were in HIV-positive individuals, who are particularly susceptible to TB. Mycobacterium tuberculosis, the bacterium that causes TB, is spread in airborne droplets when people with active disease cough or sneeze. The characteristic symptoms of TB include a cough, weight loss, and night sweats. Diagnostic tests for TB include microscopic examination of sputum (mucus coughed up from the lungs), growth (culture) of M. tuberculosis from sputum, and molecular tests (for example, the automated Xpert MTB/RIF test) that rapidly and accurately detect M. tuberculosis in sputum and determine its antibiotic resistance. TB can be cured by taking several antibiotics daily for at least six months, although the emergence of multidrug-resistant TB is making the disease harder to treat.

Why Was This Study Done?

 

To improve TB control, active disease needs to be diagnosed and treated quickly. However, sputum microscopy, the mainstay of TB diagnosis in many high-burden settings, fails to identify up to half of infected people, and mycobacterial culture (the “gold standard” of TB diagnosis) is slow and often unavailable in resource-limited settings. In late 2010, the World Health Organization recommended the routine use of the Xpert MTB/RIF test (Xpert) for TB diagnosis, and several low- and middle-income countries are now scaling up access to Xpert in their national TB control programs. But although Xpert performs well in ideal conditions, little is known about the impact of its implementation in routine (real-life) settings. In this pragmatic cluster-randomized trial, the researchers assess the health impacts of Xpert in a large TB/HIV primary health care clinic in South Africa, an upper-middle-income country that began to scale up access to Xpert for individuals showing symptoms of TB (individuals with presumptive TB) in 2011. A pragmatic trial asks whether an intervention works under real-life conditions; a cluster-randomized trial randomly assigns groups of people to receive alternative interventions and compares outcomes in the differently treated “clusters.”

What Did the Researchers Do and Find?

 

The researchers assigned everyone with presumptive TB attending a TB/HIV primary health care clinic in Cape Town to receive either Xpert for TB diagnosis or routine sputum microscopy and limited culture. Specifically, Xpert was requested on the routine laboratory request forms for individuals attending the clinic during randomly designated Xpert weeks but not during randomly designated routine testing weeks. During the 51-week trial, 982 individuals were assigned to the Xpert arm, and 1,003 were assigned to the routine testing arm, but because clinic staff sometimes failed to request Xpert during Xpert weeks, only 882 participants in the Xpert arm received the intervention. In an “intention to treat” analysis (an analysis that considers the outcomes of all the participants in a trial whether or not they received their assigned intervention), 13% of bacteriologically confirmed TB cases in the Xpert arm did not initiate TB treatment by three months after enrollment (the trial's primary outcome) compared to 25% in the routine testing arm. The proportion of participants with microbiologically confirmed TB and the proportion initiating TB treatment were higher in the Xpert arm than in the routine testing arm. Finally, the time to treatment initiation was lower in the Xpert arm than in the routine testing arm, particularly among HIV-infected participants.

What Do These Findings Mean?

 

These findings show that, in this primary health care setting, the provision of Xpert for TB diagnosis in individuals with presumptive TB provided benefits over testing that relied primarily on sputum microscopy. Notably, these benefits were seen even though a substantial proportion of individuals assigned to the Xpert intervention did not actually receive an Xpert test. The pragmatic nature of this trial, which aimed to minimize clinic disruption, and other aspects of the trial design may limit the accuracy and generalizability of these findings. Moreover, further studies are needed to discover whether the use of Xpert in real-life settings reduces the burden of TB illness and death over the long term. Nevertheless, these findings suggest that the implementation of Xpert has the potential to improve the outcomes of TB control programs and may also improve outcomes for individuals.

 

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The how, what and why of the latest HIV vaccine trial in South Africa

The how, what and why of the latest HIV vaccine trial in South Africa | IDM News | Scoop.it
For the next five years South Africa will be leading one of the latest large-scale trials for a vaccine for HIV.
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A conversation with our very own Linga-Gael Bekker
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Immunization with HIV gp140 Boosts Immune Responses Primed by MVA or DNA

Background 

The safety and immunogenicity of SAAVI DNA-C2 (4 mg IM), SAAVI MVA-C (2.9 x 10 9 pfu IM) and Novartis V2-deleted subtype C gp140 (100 mcg) with MF59 adjuvant in various vaccination regimens was evaluated in HIV-uninfected adults in South Africa. 


Methods 

Participants at three South African sites were randomized (1:1:1:1) to one of four vaccine regimens: MVA prime, sequential gp140 protein boost (M/M/P/P); concurrent MVA/gp140 (MP/MP); DNA prime, sequential MVA boost (D/D/M/M); DNA prime, concurrent MVA/gp140 boost (D/D/MP/MP) or placebo. Peak HIV specific humoral and cellular responses were measured. 


Results 

184 participants were enrolled: 52% were female, all were Black/African, median age was 23 years (range, 18–42 years) and 79% completed all vaccinations. 159 participants reported at least one adverse event, 92.5% were mild or moderate. Five, unrelated, serious adverse events were reported. The M/M/P/P and D/D/MP/MP regimens induced the strongest peak neutralizing and binding antibody responses and the greatest CD4+ T-cell responses to Env. All peak neutralizing and binding antibody responses decayed with time. The MVA, but not DNA, prime contributed to the humoral and cellular immune responses. The D/D/M/M regimen was poorly immunogenic overall but did induce modest CD4+ T-cell responses to Gag and Pol. CD8+ T-cell responses to any antigen were low for all regimens. 


Conclusions 

The SAAVI DNA-C2, SAAVI MVA-C and Novartis gp140 with MF59 adjuvant in various combinations were safe and induced neutralizing and binding antibodies and cellular immune responses. Sequential immunization with gp140 boosted immune responses primed by MVA or DNA. The best overall immune responses were seen with the M/M/P/P regimen. 

Ed Rybicki's insight:
Brand new HIV vaccine trial result out of South Africa - and the IDM!
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Ed Rybicki's curator insight, September 6, 2016 4:47 AM
Brand new HIV vaccine trial - out of South Africa AND with my favourite virologist on it B-)
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New Zika Mouse Model Mimics Human Disease

New Zika Mouse Model Mimics Human Disease | IDM News | Scoop.it
Researchers develop another mouse model of Zika virus infection that mimics the disease in humans.
Ed Rybicki's insight:
...and strains from Africa, Polynesia and Asia were used in it - and all did the same thing?  Interesting...meaning there is no clear differentiation between "original" (=older) African strains and more recent incarnations?  Meaning, obviously, that background immunity due to endemicity will probably prevent the nastiness seen in adult infections in S America?  Possibly...watch this space!
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The Frightening Thing About a Virus That Kills Farmed Fish

The Frightening Thing About a Virus That Kills Farmed Fish | IDM News | Scoop.it
Zika and Ebola get all the headlines, but pathogens that threaten livestock and crops could be even more dangerous for humans.  
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Amen.  That's why we're starting to work on fish now B-)
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ProMED-mail Ebola updateSigh...wha

Ebola re-emerges in Liberia with woman's death
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Lab tests have confirmed a new Ebola infection in Liberia, involving a 30-year-old woman who died yesterday [30 Mar 2016] during transfer from a clinic to a hospital in Monrovia, according to a statement today from the World Health Organization (WHO).

Health officials immediately sent a team to launch an investigation and trace contacts in the community outside Monrovia where the woman lived and had been treated at a clinic, the WHO said. Also, Liberian officials convened an emergency meeting today [1 Apr 2016] to coordinate the response.

Two countries addressing flare-ups
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Liberia becomes the 2nd country in the outbreak region -- alongside Guinea -- to report re-emergence of the disease. The new case seems to underscore a warning earlier this week [week of 28 Mar 2016] from WHO officials that despite the end of the public health emergency of international concern for Ebola, sporadic cases are likely to occur because of lingering virus in the survivor population.

Liberia's flare-up is the country's 3rd since its initial outbreak was declared over in May 2015. Its most recent cluster occurred in November 2015 and ended in the middle of January [2016].

Confirmation of Liberia's latest case marks the region's 13th recurrence of the disease. The Ebola virus can linger in immune-protected parts of the body, such as eyes and testes, and sexual transmission has been suspected as the source of some recent illness clusters.

Over 1000 contacts in Guinea
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Neighboring Guinea is battling an outbreak centered near a village in the southern Nzerekore district, where 9 cases and 7 deaths have been reported [since late February 2016].

In a recent update on the response to Guinea's Ebola cluster, the WHO said more than 1000 contacts have been identified and nearly 800 were immunized with VSV-EBOV [vesicular stomatitis virus-Ebola virus vaccine] in a ring vaccination campaign that it is coordinating. In a large earlier trial in Guinea, VSV-EBOV, developed by Canadian scientists and licensed by NewLink Genetics and Merck, was found to be highly effective, and it has been tested and deployed in other Ebola clusters.

The WHO has sent a 75-member team to help local officials in Guinea, as well as 2 clinicians to help in Nzerekore's Ebola treatment center.
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Sigh...what did I say??
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Cameroon alarmed by fake yellow fever vaccine

The Cameroonian government has issued a warning, urging officials of the national drugs supply structures and public and management of private health facilities to ensure that the falsified versions of the vaccine “Amaril stabilized” against yellow fever is not in their stocks.Coming from the Pasteur Institute in Dakar under the lot number 2265 and June 2017 as expiry date, the manufacturer said he has found errors and other irregularities on the package, which results laboratory tests are not known yet.

The institutions having such product in their stocks are invited to stop distributing and to isolate the vaccine, authorities urged.
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Nasty, that: on the heels of fake vaccination certificates issued in Nigeria...
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Scientists investigate the weird genetics of bat wings

Scientists investigate the weird genetics of bat wings | IDM News | Scoop.it
A bat in flight is a marvelous sight — but we don't really know how they got their wings.
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Great work - and partly from UCT!
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Why taking vitamin D pills can help the fight against TB and HIV

Why taking vitamin D pills can help the fight against TB and HIV | IDM News | Scoop.it
In countries such as South Africa with a high burden of TB and HIV, vitamin D could be an extremely effective and cheap weapon to include in the arsenal against TB and HIV.
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Groundbreaking stuff from South Africa!
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UCT's biotech lab takes drug discovery to new level

UCT's biotech lab takes drug discovery to new level | IDM News | Scoop.it

The recent launch of H3D’s state-of-the-art, R22 million medicinal chemistry laboratory marks a new chapter in the university’s drug discovery programme.


Launched under the umbrella of UCT’s Drug Discovery and Development Centre’s (H3D), the new laboratory underscores the Western Cape’s reputation as the biotech hub of Africa.

H3D was founded in 2011 to create a discovery and development platform for new drugs and is Africa’s first fully integrated modern drug discovery and development centre. In 2012 the first compound was approved by Medicines for Malaria Venture (MMV) as a preclinical, anti-malarial development candidate. It has now completed Phase I human trials.

H3D has also boosted its scientific staff in the areas of medicinal chemistry, biology, drug metabolism and pharmacokinetics. The team now includes five top scientists from the biotech industry and pharmaceutical companies AstraZeneca and Merck. Between them they have a combined 110 years of biotech and pharmaceutical industry drug discovery experience.

This means the centre now has the integrated skills and infrastructure comparable to a biotech or pharmaceutical company needed to produce new drug candidates for life-threatening diseases, says H3D founder and director, Professor Kelly Chibale (chemistry department).

 
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Profile: South Africa's Emavundleni Research Centre for HIV

When The Lancet visited the Emavundleni Research Centre in Cape Town's New Crossroads township, it was difficult to see how a modern research facility could exist in the backdrop of such startling poverty. But the bright, modern centre, under the leadership of Linda-Gail Bekker, and a joint venture of the Desmond Tutu HIV Foundation and the University of Cape Town, has established itself as part of the community and recently celebrated its tenth anniversary.The centre started life in a converted shipping container before it moved to its existing premises, and continues to grow apace. It is equipped with full testing facilities for HIV and other sexually transmitted diseases, as well as a pharmacy with deep cold units for safely storing products. There are a suite of consultation rooms in which the women and men that form the backbone of their clinical trials receive counselling and treatment.
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Challenges in the Design of a T Cell Vaccine in the Context of HIV-1 Diversity

Challenges in the Design of a T Cell Vaccine in the Context of HIV-1 Diversity | IDM News | Scoop.it

Abstract: The extraordinary variability of HIV-1 poses a major obstacle to vaccine development. The effectiveness of a vaccine is likely to vary dramatically in different populations infected with different HIV-1 subtypes, unless innovative vaccine immunogens are developed to protect against the range of HIV-1 diversity. Immunogen design for stimulating neutralizing antibody responses focuses on “breadth” – the targeting of a handful of highly conserved neutralizing determinants on the HIV-1 Envelope protein that can recognize the majority of viruses across all HIV-1 subtypes. An effective vaccine will likely require the generation of both broadly cross-neutralizing antibodies and non-neutralizing antibodies, as well as broadly cross-reactive T cells. Several approaches have been taken to design such broadly-reactive and cross-protective T cell immunogens. Artificial sequences have been designed that reduce the genetic distance between a vaccine strain and contemporary circulating viruses; “mosaic” immunogens extend this concept to contain multiple potential T cell epitope (PTE) variants; and further efforts attempt to focus T cell immunity on highly conserved regions of the HIV-1 genome. Thus far, a number of pre-clinical and early clinical studies have been performed assessing these new immunogens. In this review, the potential use of these new immunogens is explored. 

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From our own crew!

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