Stewardship / Resistance Scan for Feb 08, 2018

News brief

Study indicates yaws elimination strategy needs modification

A longitudinal study in Papua New Guinea has found that mass administration of antibiotics followed by targeted treatment did not eliminate yaws, researchers reported yesterday in The Lancet. The study also discovered the first signs of resistance in the tropical infection, which causes chronic disfiguring skin ulcers in children in at least 14 countries.

The World Health Organization's strategy to eliminate yaws, an infectious disease caused by Treponema pallidum subspecies pertenue (T p pertenue), is the mass administration of a single dose of azithromycin aiming for a population coverage of more than 90%, followed by active case detection surveys every 3 to 6 months. Previous studies had found that mass treatment with azithromycin was associated with a nearly 90% reduction of serologically-confirmed active yaws from 2.4% to 0.3%, but long-term efficacy has not been determined.

From April 2013 through October 2016, the researchers studied the population of Lihir, an island of Papua New Guinea where yaws is endemic. They found that mass azithromycin treatment followed by targeted treatment programs reduced the prevalence of active yaws from 1.8% to 0.1% at 18 months, but the infection began to re-emerge at 24 months and the prevalence climbed to 0.4% at 42 months. Most of the cases were latent infections in individuals who were absent at the time of mass treatment, but some were imported.

In addition, the researchers found five cases of yaws at months 36 and 42 that were resistant to azithromycin. Polymerase chain reaction testing indicated that the resistance was caused by mutations in the 23S ribosomal RNA gene. All the cases were from the same village, indicating infection with the same strain.

"Our study underlines the need to treat every individual living in an endemic zone, in order to cure latent infections," lead author Oriol Mitja, MD, said in a press release from the Barcelona Institute for Global Health. Mitja and his colleagues conclude that a distribution of a second or third round of azithromycin at 6 to 12 months might be of substantial benefit.
Feb 7 Lancet abstract
Feb 7 Barcelona Institute for Global Health press release


Antibiotic-resistant Campylobacter implicated in 2016 raw milk outbreak

A 17-case Campylobacter outbreak linked to raw milk in Colorado in August 2016 has been confirmed to be caused by C jejuni bacteria resistant to fluoroquinolones, a class of antibiotics often used to treat campylobacteriosis, scientists from Colorado and the Centers for Disease Control and Prevention reported today in Morbidity and Mortality Weekly Report (MMWR).

Health officials confirmed 12 cases, and 5 other were deemed probable. Patients ranged in age from 12 to 68, with a median age of 58, and 9 were male. Illnesses lasted from 3 to 10 days, and one person required hospitalization. Testing of samples from patients and unpasteurized milk from the source dairy revealed matching C jejuni pathogens.

The National Antimicrobial Resistance Monitoring System performed antimicrobial susceptibility tests on five representative isolates, and all were resistant to ciprofloxacin, tetracycline, and nalidixic acid.

The authors concluded, "All tested isolates' resistance to three antibiotics was concerning, particularly as fluoroquinolones are frequently used to treat Campylobacter infections in those cases where treatment is indicated. Treatment of antibiotic-resistant Campylobacter infections might be more difficult, of longer duration, and possibly lead to more severe illness than treatment of nonresistant Campylobacter infections." The noted that, in 2015, 25.3% of US C jejuni isolates were resistant to ciprofloxacin, an increase from 21.6% 10 years earlier.
Feb 9 MMWR report

News Scan for Feb 08, 2018

News brief

Phase 3 study of smallpox vaccine meets study end points

Bavarian Nordic today announced promising findings for a phase 3 study of its smallpox vaccine Imvamune, which compared its efficacy against ACAM200, the smallpox vaccine currently licensed in the United States. Imvamune is a nonreplicating vaccine designed to be safer for use in patients who shouldn't be given the replicating vaccine, such as those with atopic dermatitis or HIV.

The open-label study of 440 volunteers at a US military facility in South Korea by a team from the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) showed that peak neutralizing antibodies were twice as high as with ACAM2000, which met one of the two study end points and suggested the vaccine prompted a statistically superior immune response, according to a company news release. The study also looked at the vaccine's ability to prevent or attenuate a pustule, scab, or scar in people vaccinated with the second dose. The study found that primary vaccination with Imvamune reduced lesion size and prevented lesions in most subjects revaccinated with ACAM2000.

The study is the second phase 3 study to support a favorable safety profile and efficacy when compared with replicating smallpox vaccines, the company said, and paves the way for it to apply for licensing with the US Food and Drug Administration (FDA) in the last half of this year. If the vaccine is approved, Bavarian Nordic would be eligible for a priority review voucher that it could use to streamline the review of a future license application or transfer to another company.

Paul Chaplin, Bavarian Nordic's president and chief executive officer, said in the release, "This program has only been possible through the consistent and strong support of numerous U.S. Government agencies and demonstrates what can be achieved through a successful public-private partnership to protect the public from the deliberate release of the smallpox virus."

Col Gary Wheeler, commander of USAMRIID, said in a USAMRIID press release, "If approved, this vaccine will have a direct impact on improving force health protection for U.S. Soldiers and other service members who are required to be immunized against smallpox."

The company has already delivered 28 million of liquid-frozen Imvamune to the US Strategic National Stockpile for emergency use and has a contract to replenish the stockpile with a freeze-dried formation to extend the vaccine's shelf life.
Feb 8 Bavarian Nordic press release
Feb 8 USAMRIID press release


Incubation period for Salmonella cases often outside 'standard' range

Minnesota health officials report that, although the incubation period for Salmonella infection is often reported as ranging from 6 to 72 hours (3 days), 40% of culture-confirmed infections involved shorter or longer incubation periods, some as long as 16 days, according to their data published yesterday in Epidemiology & Infection.

The investigators combed through data on Minnesota salmonellosis outbreaks from 2000 through 2015, noting that 725 cases (out of 1,517) had enough data to calculate a precise incubation period—the time from exposure to first symptoms. Of those cases, 425 (59%) were culture-confirmed.

For all 725 cases, the time from exposure to onset of first symptom was 45 hours and to onset of an objective symptom was 49 hours. More than two-thirds (491, 68%) had incubation periods within the commonly referenced range of 6 to 72 hours, and 249 cases (34%) had incubation periods of 12 to 36 hours, which is often called the "usual" range.

The researchers determined that 65 cases (9%) had incubations less than 12 hours and 23 (3%) had incubations less than 6 hours. In addition, 211 cases (29%) had incubation periods longer than 72 hours, including 124 (17%) from 72 to 120 hours (5 days), 52 (7%) from 121 to 168 hours, and 35 (5%) longer than 168 hours (7 days)—most in the 8-to-9-day range but several in the 10-to-16-day range.

The authors also reported that culture-confirmed cases had significantly longer median periods to first symptom (54.5 vs. 29.8 hours) and to first objective symptom (62.5 vs. 35.5 hours) compared with the other cases. Of the culture-confirmed cases, only 60% involved incubation periods within the 6-to-72-hour range.
Feb 7 Epidemiol Infect abstract

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