News Scan for Sep 25, 2018

News brief

Adjuvanted TB vaccine shows promise in curbing active infections

A phase 2 study of an adjuvanted subunit vaccine against tuberculosis (TB) in young and middle-aged adults with the latent form of the disease found that it was 54% effective against progression to the active pulmonary form of the disease. An international team led by scientists from GlaxoSmithKline, the vaccine's developer, reported its findings today in the New England Journal of Medicine.

An effective vaccine for preventing full-blown TB in people already infected with Mycobacterium tuberculosis has long been a goal in efforts to reduce the impact of the world's leading infectious cause of death, especially against the backdrop of rising numbers of multidrug-resistant cases. Studies have suggested that a vaccine targeted to adolescents and adults would be the most potent tool in driving down TB levels.

The trial of the M72/AS01E vaccine took place in Kenya, South Africa, and Zambia, enrolling adults ages 18 to 50 with latent TB who had previously received the bacille Calmette–Guérin (BCG) vaccine. Of the group, 1,786 received two vaccine doses given 1 month apart and 1,787 received placebo.

After 2.3 years of follow-up, the researchers found that 10 who received the adjuvanted vaccine progressed to active TB, compared with 22 in the placebo group. Vaccine efficacy was 54% (90% confidence interval [CI], 13.9% to 75.4%; 95% CI, 2.9% to 78.2%, P = 0.04). There were more reports of adverse events in the TB vaccine group 30 days after injection, mainly injection-site reactions and flulike symptoms.

In an accompanying editorial, Barry Bloom, PhD, with the Harvard T.H. Chan School of Public Health in Boston, wrote that trials of new TB vaccines have been disappointing, but the findings for M72/AS01E established proof of principle. He noted that the study found greater protection in those age 25 and younger and in men.

Bloom said the vaccine's greater effectiveness compared with an earlier subunit vaccine candidate suggests that the adjuvant may be critical, "an important finding in itself."

Though the findings suggest a promising intervention in the age-group that could play a key role in reducing the global TB burden, he said several questions remain, such as immunologic and gene-expression differences in those who were and weren't protected, defining the role of previous BCG vaccination and latent TB on efficacy, whether including more M tuberculosis antigens could improve the 54% efficacy, and what results might be in other populations.
Sep 25 N Engl J Med abstract
Sep 25 N Engl J Med editorial


CDC: Congenital syphilis surges to 20-year high

Syphilis infections passed from mothers to babies during pregnancy or delivery have more than doubled since 2013, which suggests gaps in prenatal care and routine testing for the disease, especially in women who are at high risk, the US Centers for Disease Control and Prevention (CDC) said today.

The CDC based its findings on data from its annual Sexually Transmitted Disease Surveillance Report, released today. The agency said congenital syphilis cases spiked from 362 in 2013 to 918 in 2017, the most in 20 years. Cases were reported in 37 states, mostly in the West and South.

Rising syphilis in newborns mirrors a rise in reproductive-age women and is outpacing overall national increases in sexually transmitted diseases, according to the new findings.

Jonathan Mermin, MD, MPH, director of the CDC's National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, said in a CDC statement that congenital syphilis can result in miscarriage, newborn death, and severe lifelong physical and mental health problems. "No parent should have to bear the death of a child when it would have been prevented with a simple test and safe treatment."

The CDC said it's critical for all pregnant women to visit a health provider as soon as possible and be tested for syphilis. Without screening, a woman may not know that she has syphilis and that her baby is at risk. It added that the disease is early cured with appropriate antibiotic treatment, and that when left untreated, the risk of passing syphilis to the baby is as high as 80%.

Getting tested once during pregnancy may not be enough, given other CDC findings that showed 1 in 3 women who passed syphilis to their babies in 2016 had been tested, suggesting they contracted the disease after the test or didn't get treated in time to protect the baby. The CDC urges that women who live in high-prevalence areas be tested not only at the first prenatal visit, but also during the third trimester and at delivery.

Also, the CDC said that sexually active people can lower the risk of getting syphilis by being in a long-term, mutually monogamous relationship with a partner who has been tested and by using condoms the right way every time during sex. It added that it is stepping up support for high-burden states to improve testing, is doing research on factors contributing to the resurgence, and is increasing awareness among pregnant women though partners such as the March of Dimes.
Sep 25 CDC press release


NIH adds 5 clinical sites to Undiagnosed Disease Network

The National Institutes of Health (NIH) expanded the Undiagnosed Disease Network (UDN) through the addition of five clinical sites, bringing the total number of UDN sites to 12. The expansion is part of UDN's phase 2 plan, and will cost approximately $100 million over the next 4 years.

In a press release yesterday, the NIH said the expansion will allow more patients with rare, difficult diseases across the country access to UDN's cutting edge technology, including genomic sequencing and metabolomics. The goal of the UDN is to more quickly diagnose and treat patients with unknown diseases.

The new sites are the Children's Hospital of Philadelphia and the Hospital of University of Pennsylvania; the University of Miami School of Medicine; the University of Utah, Salt Lake City; the University of Washington School of Medicine, Seattle and the Seattle Children's Hospital; and Washington University in St. Louis.

"The UDN takes advantage of cutting-edge technologies such as genomic sequencing, metabolomics and assessing patient variants in model organisms to give clinicians new, powerful information to help understand the cause of extremely rare diseases," said Anastasia L. Wise, PhD, program director for the UDN in the National Human Genome Research Institute's Division of Genomic Medicine.
Sep 24 NIH
press release


H5N6 avian flu strikes poultry in northern Vietnam

Vietnam's agriculture ministry today reported a highly pathogenic H5N6 avian flu outbreak in village poultry in Cao Bang province in the north, according to a notification from the World Organization for Animal Health (OIE).

The event began on Sep 14 and killed 200 of 6,803 susceptible poultry, and the remaining birds were culled to control the spread of the virus. Poultry vaccination was also ordered as part of the outbreak response.

So far, the source of the outbreak isn't known. The highly pathogenic H5N6 virus circulating in poultry in a handful of Asian countries has been linked to some human infections, which have often been fatal. Vietnam reported its last H5N6 outbreaks in early August, which struck three locations, one in Nghe An province and two in Hai Phong province.
Sep 25 OIE report

Stewardship / Resistance Scan for Sep 25, 2018

News brief

Antifungal stewardship tied to an 89% drop in inappropriate prescribing

A small single-center UK study has demonstrated that a diagnostics-driven antifungal stewardship (AFS) program was tied to an 89% drop in inappropriate prescribing, according to a study yesterday in the Journal of Antimicrobial Chemotherapy.

University of Manchester researchers assessed the AFS program at Wythenshawe Hospital, which has been developed over the past 8 years. It includes: (1) updating and clarifying antifungal guidelines, (2) involving and educating stewardship champions, (3) improving access to timely diagnostic testing, and (4) reducing unnecessary antifungal use.

The study included all patients who were prescribed micafungin for suspected or proven invasive candidiasis during 4-month audit periods in 2014 and 2016. The team reviewed prescriptions and patient records against AFS guidelines, as well as antifungal consumption and mortality data.

The investigators found that the number of patients treated for invasive candidiasis decreased from 39 in 2014 to 29 in 2016, mainly because of a reduction in patients initiated on antifungal therapy inappropriately—18 in 2014 and only 2 in 2016, an 89% drop. Antifungal therapy was stopped following negative biomarker results in 12 patients in 2014 and 10 patients in 2016. Crude mortality caused by proven or probable invasive candidiasis decreased from 45% to 19% (a 58% reduction), and antifungal consumption dropped by 49%.
Sep 24 J Antimicrob Chemother study


CARB-X calls for open data sharing to spur antibiotic innovation

Kevin Outterson, JD, the executive director of CARB-X, is calling on antibacterial researchers around the world to "help others learn from their setbacks" by openly sharing data from unsuccessful research in an effort to accelerate development to combat drug-resistant infections, CARB-X said in a news release yesterday.

As part of this effort, CARB-X (Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator), a public-private partnership, has reached an agreement with Achaogen to the non-exclusive transfer of compounds, scientific data, and assays to Forge Therapeutics from its innovative LpxC program. Achaogen announced last year that it had stopped the early development program over unexpected toxicity findings. Forge plans to review Achaogen's body of LpxC knowledge and apply the findings to its on-going LpxC research program.

Using a different chemistry approach than Achaogen, Forge is developing a novel class of antibiotics to treat gram-negative bacteria such as Pseudomonas aeruginosa and multidrug-resistant Enterobacteriaceae.

"Science is hard; most projects end for any number of reasons," Outterson said. "Typically, this knowledge and even the compounds themselves would be shuttered and locked away after a project is stopped. Given the economic realities of antibacterial research and the urgent need for new antibiotics, we need to adopt a more collaborative approach where it makes sense to do so."

CARB-X is encouraged by public data-sharing initiatives like the SPARK initiative announced by PEW Charitable Trusts last year and Wellcome Trust's Open Research initiative, launched in 2016, according to the release.
Sep 24 CARB-X news release

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