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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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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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Genetically engineered 'plantibodies' to halt Ebola ?

Genetically engineered 'plantibodies' to halt Ebola ? | IDM News | Scoop.it

While little can be done to curb the current outbreak of Ebola in Africa, when the next outbreak happens, the world will be armed with cheap but powerful biologics made using plants, says UCT plant biotechnologist Professor Ed Rybicki.

 
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UCT TB and HIV researcher gets high praise from SA science academy

One of UCT's rising academic stars was recently acknowledged for her research into HIV/AIDS and tuberculosis (TB) epidemics.

The Academy of Science of South Africa (ASSAf), on behalf of the African Union (AU) Commission, The World Academy of Science (TWAS) and the Department of Science and Technology, presented Dr Keren Middelkoop with the AU-TWAS Young Scientist in South Africa award. Middelkoop won in the Life and Earth Sciences category.

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Reprieve for HIV Vaccines?

Reprieve for HIV Vaccines? | IDM News | Scoop.it
ALVAC-HIV and AIDSVAX resurected in promising South Africa Trial of the two HIV Vaccines

A new trial of the ALVAC-HIV + AIDSVAX HIV vaccine regimen, conducted in South Africa, has demonstrated its safety and a robust immune response amongst 100 healthy adults. This trial, named HVTN 097, comes in the wake of the high-profile disappointment for the vaccine combo in 2009 wherein an 18,000 strong trial conducted in Thailand demonstrated just 31% efficacy in reducing HIV transmission amongst participants, the RV144 trial or Thai Trial.

Ed Rybicki's insight:

Listened to these results at the recent HIVR4P conference in Cape Town - interesting BUT there is no efficacy reported, which is not surprising as it hasn't been investigated yet - and the subtypes do not match the southern African epidemic.

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A Dead-End Host: is there a way out? A position piece on the Ebola virus outbreak

A Dead-End Host: is there a way out? A position piece on the Ebola virus outbreak | IDM News | Scoop.it
A Dead-End Host: is there a way out? A position piece on the Ebola virus outbreak by the International Union of Immunology Societies

 

Graphic by Russell Kightley Media

Ed Rybicki's insight:

From one of our own!

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Karen Sliwa: cardiology from the heart of South Africa

Karen Sliwa: cardiology from the heart of South Africa | IDM News | Scoop.it
Karen Sliwa: cardiology from the heart of South Africa. By - Richard Lane
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UCT professors bag three wins at NSTF-BHP Billiton Awards

UCT professors bag three wins at NSTF-BHP Billiton Awards | IDM News | Scoop.it

UCT professors bag three wins at NSTF-BHP Billiton Awards

 

Three academics from the University of Cape Town have been honoured at the 16th Annual National Science and Technology Forum Annual National Science and Technology Forum (NSTF)-BHP Billiton Awards for their contributions to the fields of science, engineering, technology and innovation in South Africa.

 

The winners were announced at a gala dinner on 3 July 2014, while eight other UCT academics were among the 56 finalists for the prestigious awards.

 

Emeritus Professor Eric Bateman, Director and Founder of the UCT Lung Institute, Department of Medicine, received the accolade for an individual who has made an excellent contribution to science, engineering and technology over a lifetime.

 

Professor Keertan Dheda, Head of the Division of Pulmonology, Department of Medicine, was recognised for his exceptional support of the fields of science, engineering and technology through research and its outputs over the last five to ten years.

 

The third award went to Associate Professor Arnaud Malan at UCT's Department of Mechanical Engineering. The award recognised an individual or a team for an outstanding contribution to science, engineering and technology through research leading to innovation in a corporate organisation or institution. He is primarily responsible for developing Elemental software, which is described as a giant leap for technology.

 

Click here to read full article.


Via UCT Research Office News
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The Journal for Virology

"

 The Journal for Virology is world's most read journal  in the area of Virology

The Journal for Virology accepts reviews and original research articles leading towards development of knowledge and inspiration.
You can submit: Research article, Review, Letter, Technical/ Scientific write up/ paper/ report, Discovery, News,Conference/ Seminar/  Workshop, Proceedings, and ideas.
Ed Rybicki's insight:

Yeah.  Sure.  I'll get right on getting my msssss. ready....

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A novel papillomavirus in Adélie penguin faeces in Antarctica

Papillomaviruses are epitheliotropic viruses that have circular dsDNA genomes encapsidated in non-enveloped virions. They have been found to infect a variety of mammals, reptiles and birds, but so far they have not been found in amphibians. Using a next-generation sequencing de novo assembly contig-informed recovery, we cloned and Sanger sequenced the complete genome of a novel papillomavirus from the faecal matter of Adélie penguins (Pygoscelis adeliae) nesting on Ross Island, Antarctica. The genome had all the usual features of a papillomavirus and an E9 ORF encoding a protein of unknown function that is found in all avian papillomaviruses to date. This novel papillomavirus genome shared ~60 % pairwise identity with the genomes of the other three known avian papillomaviruses: Fringilla coelebs papillomavirus 1 (FcPV1), Francolinus leucoscepus papillomavirus 1 (FlPV1) and Psittacus erithacus papillomavirus 1. Pairwise identity analysis and phylogenetic analysis of the major capsid protein gene clearly indicated that it represents a novel species, which we named Pygoscelis adeliae papillomavirus 1 (PaCV1). No evidence of recombination was detected in the genome of PaCV1, but we did detect a recombinant region (119 nt) in the E6 gene of FlPV1 with the recombinant region being derived from ancestral FcPV1-like sequences. Previously only paramyxoviruses, orthomyxoviruses and avian pox viruses have been genetically identified in penguins; however, the majority of penguin viral identifications have been based on serology or histology. This is the first report, to our knowledge, of a papillomavirus associated with a penguin species.

 
Ed Rybicki's insight:

Nice to see his learning put to good: well done, Arvind and colleagues!

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HPV type 16 E7 protein bodies cause tumour regression in mice

HPV type 16 E7 protein bodies cause tumour regression in mice | IDM News | Scoop.it

Background

Human papillomaviruses (HPV) are the causative agents of cervical cancer in women, which results in over 250 000 deaths per year. Presently there are two prophylactic vaccines on the market, protecting against the two most common high-risk HPV types 16 and 18. These vaccines remain very expensive and are not generally affordable in developing countries where they are needed most. Additionally, there remains a need to treat women that are already infected with HPV, and who have high-grade lesions or cervical cancer.

Methods

In this paper, we characterize the immunogenicity of a therapeutic vaccine that targets the E7 protein of the most prevalent high-risk HPV - type 16 - the gene which has previously been shown to be effective in DNA vaccine trials in mice. The synthetic shuffled HPV-16 E7 (16E7SH) has lost its transforming properties but retains all naturally-occurring CTL epitopes. This was genetically fused to Zera(R), a self-assembly domain of the maize gamma-zein able to induce the accumulation of recombinant proteins into protein bodies (PBs), within the endoplasmic reticulum in a number of expression systems.

Results

High-level expression of the HPV 16E7SH protein fused to Zera(R) in plants was achieved, and the protein bodies could be easily and cost-effectively purified. Immune responses comparable to the 16E7SH DNA vaccine were demonstrated in the murine model, with the protein vaccine successfully inducing a specific humoral as well as cell mediated immune response, and mediating tumour regression.

Conclusions

The fusion of 16E7SH to the Zera(R) peptide was found to enhance the immune responses, presumably by means of a more efficient antigen presentation via the protein bodies. Interestingly, simply mixing the free PBs and 16E7SH also enhanced immune responses, indicating an adjuvant activity for the Zera(R) PBs.

 

I thank Russell Kightley Media for use of the HPV/cervical cancer graphic

Ed Rybicki's insight:

I keep saying - you gotta go green...B-) And here we are, suiting action to words.  

Modestly, of course.  

Well done to Mark Whitehead and Thomas Oelschlager; thanks to Inga for sticking with a difficult ms - and thanks Era Biotech for the technology!

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Colin Kaplan, Virologist: RIP

Colin Kaplan, Virologist: RIP | IDM News | Scoop.it

Born in Durban, Colin Kaplan followed his older brother Cyril to the University of Cape Town, where he was an avid member of the University Mountain Club. He met his wife Felicity at a Communist Party rally in 1942. After internships at the University’s Groote Schuur Teaching Hospital he became a lecturer in the department of pathology, until the 1948 introduction of racist apartheid legislation by South Africa’s nationalist government persuaded him to bring his family to England. Appointed lecturer in the bacteriology department at University College Hospital and then as a bacteriologist at the Lister Institute of Preventive Medicine, he pioneered a programme to accelerate the production of freeze dried smallpox vaccine, becoming head of the virus vaccine department. In 1961 he began consulting for the World Health Organization, providing his expertise in smallpox vaccine production to India, which subsequently became a net exporter of the vaccine. WHO work also took him to Nepal, Thailand, Burma, Indonesia, and Sri Lanka. As a member of the WHO scientific committee on smallpox, he oversaw the global eradication of the disease in 1977, the same year Rabies: the Facts was published, which Colin coauthored. In 1968 he’d taken the chair of microbiology at Reading University, becoming dean of the faculty of science for a period and remaining at Reading until his retirement in 1986. In 1997 his book Infection and Environment was published to general acclaim, and he remains highly regarded as one of the two founding editors of the Journal of General Virology in 1967.

He leaves a daughter, two sons, and six grandchildren.

Ed Rybicki's insight:

...and he's left R1500 a year to the Division of Medical Virology at UCT for the best contribution by a young scientist!

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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. 

Ed Rybicki's insight:

From our own crew!

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Twitter coverage of IDM's 10th Anniversary Symposium

Anyone interested can trawl the tweet archive by looking for #IDM10th

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IDM Wolfson Lecture: Mark Davis

IDM Wolfson Lecture: Mark Davis | IDM News | Scoop.it

New approaches to human immunology in health and disease
5 November 2014

 

Some of the deep complexities of our immune system, once seen as a "black box" in medicine, have been demystified, but we need new approaches to reveal all its mysteries, says renowned Stanford University immunologist Professor Mark Davis.

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Ebola: A UCT researcher's experience at the frontline

Ebola: A UCT researcher's experience at the frontline | IDM News | Scoop.it

Kathryn Stinson, a UCT epidemiologist, went to Sierra Leone to help combat the Ebola epidemic and recently returned. Why did she decide to go, and what were her experiences? We've gathered her published accounts in one place:

 
Ed Rybicki's insight:

Great resource and a brave researcher.

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IDM 10th Birthday Symposium

This symposium started last night, with addresses by UCT's Vice-Chancellor Dr Max Price, the Dean of Health Sciences Prof Wim de Villiers, the President of the SA Medical Research Council Prof Glenda Gray, a Wolfson Memorial Lecture by Prof Mark Davis of Stanford and the Howard Hughes Medical Institute, and a closing address by the Minister of Science and Technology in SA, Ms Naledi Pandor.

An upbeat occasion enjoyed by all - especially during the follow-up cocktail party.

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Unexpected findings in HIV meningitis treatment trial can save lives

Unexpected findings in HIV meningitis treatment trial can save lives | IDM News | Scoop.it

UCT investigators in collaboration with Ugandan and American colleagues found that HIV patients with cryptococcal meningitis – a common AIDS-related infection – should first be fully treated for the condition in hospital, and only start antiretroviral (ARV) therapy afterwards.

These surprising findings are in contrast with worldwide HIV treatment guidelines to start ARVs as soon as possible (within two weeks) in patients with advanced HIV and AIDS. Studies in patients with HIV and tuberculosis (TB) as well as in other AIDS-related opportunistic infections have shown that this strategy improves overall survival.

The large clinical trial found that waiting five to six weeks to start ARVs after cryptococcal meningitis diagnosis resulted in 15% better survival than starting ARVs one to two weeks after diagnosis.

"The implications of these findings for when to start treatment with ARVs to maximize survival in HIV+ patients are very important," says UCT investigator Associate Professor Graeme Meintjes of the Cryptococcal Optimal Antiretroviral Timing (COAT) Trial. The findings have already informed international HIV guidelines prior to their publication in the June issue of the prestigious New England Journal of Medicine.


 
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UCT Building named after CAT scan Nobel laureate

UCT Building named after CAT scan Nobel laureate | IDM News | Scoop.it

A family man, who enjoyed solving problems and had a great sense of humour.

 

These were words Emeritus Professor Kit Vaughan used to describe the Nobel laureate at the naming of Allan Cormack House. Cormack, a nuclear physicist who studied and worked at UCT before immigrating to the US, won the Nobel Prize in Physiology or Medicine in 1979 for his contribution to the development of computed tomography or CT scanner.

 

The building named after him houses UCT's Department of Research and Innovation among others.

 

His youngest daughter Jean Cormack was present at the naming ceremony hosted by UCT registrar Hugh Amoore. Cormack, who was born in Cape Town but lives in America, was visiting her South African cousin, Jo Prentice, whose mother Amy was Allan Cormack's sister. She said she was honoured that the university had chosen to remember her father in this way.

 

Vaughan, who won the 2010 UCT Book Award for his biography of Allan Cormack, Imagining the Elephant, quoted from Cormack's acceptance speech upon receiving the Nobel Prize together with Godfrey Hounsfield: "There is irony in this award since neither Hounsfield nor I is a physician. In fact it is not much of an exaggeration to say that what Hounsfield and I know about medicine and physiology could be written on a small prescription form."

 

Vaughan noted that the speech perfectly illustrated Cormack's "self-deprecating humour and genuine humility". He donated a copy of his book to the occupants of Allan Cormack House adding that he trusts that the occupants "will take the time to find out more about the man after whom (their) building is named".

 

Story by Abigail Calata. Image by Michael Hammond.


Via UCT Research Office News
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The complete genome sequences of poxviruses isolated from a penguin and a pigeon in South Africa

Two novel avipoxviruses from South Africa have been sequenced, one from a Feral Pigeon (Columba livia) (FeP2) and the other from an African penguin (Spheniscus demersus) (PEPV). We present a purpose-designed bioinformatics pipeline for analysis of next generation sequence data of avian poxviruses and compare the different avipoxviruses sequenced to date with specific emphasis on their evolution and gene content.
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Novel avian flu virus discovered in penguins in Antarctica

Novel avian flu virus discovered in penguins in Antarctica | IDM News | Scoop.it
Scientists have discovered a new strain of avian flu in the Antarctic, after testing a group of Adélie penguins, according to an Australian-based researcher. "We found that this virus was unlike anything else detected in the world," Aeron Hurt of the World Health Organization's Collaborating Centre for Reference and Research on Influenza told Reuters from Melbourne on Tuesday. The flu virus, H11N2, was found in a small number of members of a group of Adélie penguins tested at two locations on the Antarctic Peninsula, the continent's northernmost region. The strain is described in a study published this week in mBio, the online open-access journal of American Society for Microbiology.
Ed Rybicki's insight:

On the principle that one good penguin deserves another virus...B-)  See what you were missing, Don??!

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Pets to be tested for deadly Mers coronavirus

Pets to be tested for deadly Mers coronavirus | IDM News | Scoop.it

Scientists are soon to test cats, dogs and even rats as they seek to understand the mysterious Mers infection.

Middle East Respiratory Syndrome was first discovered in 2012 and has so far killed about 200 people globally.

While the virus that causes it has been found widely in camels, researchers say it could be lurking in other species.

One expert told BBC News that the hunt was likely to extend soon to animals that had close contact with people.

Mers was originally found in a patient from Bishah in Saudi Arabia but since then almost 600 cases of the infection have been discovered around the world, with about 30% of those who get sick dying from the illness.

Researchers believe the coronavirus that causes the infection crossed over from animals.

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TB still outfoxing the human race after millennia

TB still outfoxing the human race after millennia | IDM News | Scoop.it

Hot on the TB trail: Prof Keertan Dheda outlines the challenges the medical fraternity faces when trying to diagnose a centuries-old foe – tuberculosis.

One of the leading causes of death in Africa, tuberculosis, or TB as it is commonly known, has received a great deal of media interest recently, charting the development of new treatments, and highlighting new methods of diagnosis.

The challenge around the diagnosis of TB was the subject of a recent Café Scientifique* talk presented by Professor Keertan Dheda, Director of the Lung Infection; Immunity Unit and the UCT Lung Institute, and Head of UCT's Division of Pulmonology.

 

 

Ed Rybicki's insight:

See also here: https://www.youtube.com/watch?feature=player_embedded&v=m_kKg89RoOM

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