News Scan for Nov 08, 2017

News brief

Study: H3N2 mutation in egg-based vaccines lowered efficacy

In experiments designed to discover reasons for the relatively low effectiveness of last season's flu vaccine against the H3N2 strain—despite what experts thought was a close match between the vaccine strain and circulating viruses—researchers found that the culprit was a mutation that arose during production when the virus was passaged in chicken eggs.

Researchers based at the University of Pennsylvania reported their findings yesterday in Proceedings of the National Academy of Sciences (PNAS). They found that the egg-adapted virus lacked a key glycosylation site on the hemagglutinin protein. The findings raise concerns, because the same H3N2 vaccine strain is in the 2017-18 flu vaccines and may again provide an underwhelming level of protection. Also, the investigators said the findings underscore ongoing problems with producing flu vaccine antigen in eggs and that antigens grown in systems other than eggs are more likely to protect against H3N2 viruses that are currently circulating.

As part of their study, the scientists found that antibodies elicited in ferrets and humans exposed to the egg-produced 2016-17 H3N2 strain did a poor job neutralizing the viruses that circulated last flu season. However, antibodies elicited in ferrets infected with the current circulating H3N2 strain and humans vaccinated with an H3N2 vaccine produced in a non-egg system were able to recognize and neutralize the new H3N2 virus.

On Oct 23, some of the same researchers were part of another study team based at Scripps Research Institute that described the structure of the mutation using x-ray crystallography. They reported their findings in PLoS Pathogens.

Scott Hensley, PhD, coauthor of both studies and associate professor of microbiology at the University of Pennsylvania's Perelman School of Medicine, said in press release from the school, "Our data suggest that we should invest in new technologies that allow us to ramp up production of influenza vaccines that are not reliant on eggs." Though the flu season could be another difficult one if H3N2 viruses dominate again, he said people should still get vaccinated, because some protection against H3N2 is better than nothing and the H1N1 and influenza B components will likely provide excellent protection.

Yesterday Stat News contacted several experts about current options for producing vaccines that are less likely to contain mutations introduced during the production process and obstacles to moving manufacturing away from eggs entirely. The US government has supported other flu vaccine platforms: a recombinant vaccine (FluBlok) from Protein Sciences and a cell-based vaccine (Flucelvax) made by Seqirus. Experts said obstacles include the expense and regulatory hurdles of shifting to another production method, especially since for now there is little evidence that those flu vaccines are better.
Nov 6 PNAS study
Nov 6 Penn Medicine press release
Oct 23 PLoS Pathog study
Oct 30 Scripps Research Institute press release on PLoS study
Nov 7 Stat News story

WHO weighs in on Marburg virus risk to Uganda, other areas

Uganda's Marburg virus outbreak poses a high risk to the country and neighboring African nations because of a combination of factors, including that the affected districts are near caves in Mount Elgon National Park that are a major tourist attraction and harbor fruit bats that are known to transmit the virus, the World Health Organization (WHO) said yesterday in an announcement.

The affected areas, along with the zoonotic threat, are close to the border with Kenya where cross-border movements are common, the WHO said, adding the outbreak poses a low global threat.

The risk picture requires an immediate, coordinated response with support from international partners, and officials should take note of tourism to Mount Elgon including the caves and give appropriate advice and precautions, the agency said.

Regarding the investigation into the three-case family cluster, two of them confirmed and one probable, the WHO said responders face a tough challenge given the high numbers of contacts in extended families, at healthcare facilities, and from traditional burial ceremonies. One high-risk contact of that patient, a health worker from Kween district in Uganda, has been admitted to a treatment facility. Another of the patients' close contacts reportedly traveled to Kampala, Uganda's capital, where city officials have activated a contact-tracing team.

Though the second confirmed case-patient had traveled to Kenya before he died, no human-to-human transmission has been confirmed outside of Uganda. Active case-finding is under way in the country's Kitale and West Pokot districts, and Kenya's government has activated a Marburg outbreak contingency plan and an emergency operations center.

Uganda's Ministry of Health (MOH) said in a Nov 6 statement that two people who had contact with the second confirmed case—a nurse and a driver's assistant—have tested negative for Marburg virus. Currently, authorities are monitoring 131 patients, 115 from Kween district and 16 from Kapchorwa district.
Nov 7 WHO outbreak announcement
Nov 6 Uganda MOH statement

Camel links continue in latest Saudi MERS cases

The WHO released a new update on recent MERS-CoV cases, noting that 9 out of 12 cases reported from Saudi Arabia in the month of October were linked to camel contact.

None of the cases share an epidemiologic link with other known cases. Both indirect and direct contact, including drinking raw camel milk, was implicated in the nine camel-linked cases. Camel contact is a known risk factor for MERS-CoV (Middle East respiratory syndrome coronavirus).

Since 2012, the WHO has reported 2,102 laboratory-confirmed cases of infection with MERS-CoV, including at least 733 related deaths.

In other MERS news, the World Organization for Animal Health (OIE) reported the detection of MERS-CoV on two camel farms in Taif and Buraydah. A total of 5 of 12 animals tested positive for the virus. It is not known if the animals were tested as part of an ongoing investigation into human cases.
Nov 7 WHO update
Nov 8 OIE report

Groups call for tripling of global TB research funding

Although global funding for tuberculosis (TB) research and development (R&D) reached a high of $726 million in 2016—$105 million over 2015 levels—funding for the deadly disease remains "woefully inadequate," according to a report released today by the New York City–based Treatment Action Group (TAG) and the United Nations–hosted Stop TB Partnership.

The groups launched the report, which details research funding trends from 2005 through last year, a week before high-ranking health officials from more than 90 nations convene in Moscow at the Global Ministerial Conference on Ending TB in the Sustainable Development Era. TB is the world's leading cause of death from a single pathogen, according to a TAB news release. Last month the World Health Organization estimated the disease caused 10.4 million new illnesses and killed 1.4 million people worldwide.

According to the report, funding for global TB R&D climbed steadily from $358 million in 2005 to $637 million in 2009. But from there it stagnated, ranging from $637 million to $686 million from 2009, through 2014 before dropping to $621 million in 2015. It climbed to $726 million in 2016 but was still on a plateau when adjusted for inflation.

The report's authors note, "This figure is not yet large enough for TB advocates to retire the striking statistic that TB R&D receives only one-third of the nearly $2 billion in annual funding called for by the Stop TB Partnership." They say new mechanisms for financing must be found, adding, "Actions taken in the next five years, by political leaders in office today, will determine the trajectory of TB research over the next two decades."

Lucica Ditiu, MD, executive director of the Stop TB Partnership, said in the news release, "We must raise the TB R&D topic on the political agenda, through our continuous advocacy, and the first-ever United Nations High-Level Meeting on Tuberculosis in 2018. And political commitments and discussions must translate into concrete actions. Governments must increase their spending on TB research to develop the innovations we need to end TB."
Nov 8 full report
Nov 8 TAG news release

Stewardship / Resistance Scan for Nov 08, 2017

News brief

VHA study notes rise in community-associated C diff infections

A study of Veterans Health Administration (VHA) hospitals has found that cases of community-associated Clostridium difficile infection (CA-CDI) are on the rise, researchers from the University of Texas at Austin reported yesterday in the American Journal of Infection Control.

In the retrospective cohort study of all adult VHA beneficiaries with CDI from October 2002 through September 2014, the researchers identified 30,326 patients with a first CDI episode during the 12-year period. Health care facility–onset CDI (HCFO-CDI) accounted for 60.2% of cases and was the predominant type. Among cases linked to the community, 20.6% were classified as community-onset HCFO-CDI (CO-HCFA-CDI), and 19.2% were classified as CA-CDI.

There was a shift from HCFO-CDI to CA-CDI over the study period. The proportion of patients with HCFO-CDI decreased from 73.5% during fiscal year (FY) 2003 to 53.2% during FY 2014, while CA-CDI increased from 8.3% to 26.7%.

HCFO-CDI patients, however, had worse outcomes. In multivariable models, HCFO-CDI was a positive predictor of severe CDI (odds ratio [OR], 1.71) 30-day mortality (OR, 1.46), 60-day mortality (OR, 1.48), and 90-day mortality (OR, 1.54), but was not predictive of 30-day recurrence (OR, 0.41), 60-day recurrence (OR, 0.40), and 90-day recurrence (OR, 0.41).

The authors of the study suggest the shift from HCFO-CDI to CA-CDI over the 12-year period could be caused by increasing use of high-risk antibiotics, such as fluoroquinolones, in the community, as well as increasing use of proton-pump inhibitors. They also cite an increase in the number of elderly patients admitted to long-term care facilities, which have been identified as reservoirs of CDI.
Nov 7 Am J Infect Control study

Swiss study finds NSAIDS inferior to antibiotics for treating UTIs

A randomized controlled trial by Swiss researchers has found that symptomatic treatment with non-steroidal anti-inflammatory drugs (NSAIDs) as a potential antibiotic stewardship step is inferior to antibiotic treatment in women who have uncomplicated urinary tract infections (UTIs) and is likely to be associated with increased risk of pyelonephritis.

In a study today in BMJ, the researchers randomly assigned 253 women with uncomplicated lower UTI 1:1 to treatment with diclofenac or norfloxacin. Both patients and assessors were blinded to allocation. Participants started treatment immediately after randomization and were advised to take two capsules per day. The primary outcome was symptom resolution on day 3, and the secondary outcome was the use of any antibiotic up to day 30. All participants were given a package of fosfomycin to take as a rescue antibiotic if symptoms persisted past day 3.

Resolution of symptoms at day 3 was observed in 72 (54%) of 133 women assigned to diclofenac and 96 (80%) of 120 of women assigned to norfloxacin (risk difference, 27%, P = 0.98 for non-inferiority). The median time until resolution of symptoms was 4 days in the diclofenac group and 2 days in the norfloxacin group. A total of 82 women (62%) in the diclofenac group and 118 (98%) in the norfloxacin group (98%) used antibiotics up to day 30 (risk difference, 37%, P < 0.001 for superiority). Six women in the diclofenac group received a diagnosis of pyelonephritis—a bacterial infection of the kidneys—compared with none in the norfloxacin group (P = 0.03).

Although the results show that symptomatic treatment with NSAIDs is inferior to antibiotic treatment for UTI symptom relief, the authors of the study say the fact that fewer women in the diclofenac group were on antibiotics until day 30 is important. "The observed clinically relevant reduction in antibiotic use, which would likely contribute directly to decreasing resistance rates in the affected population, suggests that alternative approaches of combining symptomatic treatment with deferred, selective antibiotic use should be developed and tested in future trials," they write.
Nov 8 BMJ study