Phase 3 trial for Takeda's dengue vaccine shows promising results

Takeda's dengue vaccine candidate (TAK-003) is safe and effective against dengue virus, according to part 1 of phase 3 clinical trial results published yesterday in the New England Journal of Medicine.

The vaccine was given to 20,000 healthy children ages 4 to 16 years in regions of Asia and Latin America where the disease is endemic. The participants were randomly given either two doses of the vaccine or placebo 3 months apart, and received their first injections between September 2016 and March 2017.

The overall vaccine efficacy was 80.9% (95% confidence interval [CI], 75.2 to 85.3; 78 cases per 13,380 [0.5 per 100 person-years]) in the vaccine group, compared with 199 cases per 6,687 (2.5 per 100 person-years) in the placebo group, the authors said.

The trivalent vaccine is based on dengue 2, and efficacy rates varied by the four dengue serotypes, with the vaccine 97.7% effective against infection with dengue 2. Efficacy was 73.7% against dengue 1, and 62.6% against dengue 3. There were not enough cases of dengue 4 to determine vaccine efficacy.

"TAK-003 was efficacious against virologically confirmed dengue fever among healthy children and adolescents 4 to 16 years of age, irrespective of previous dengue exposure," the authors concluded. "This trial is ongoing, and longer-term data will be important in better defining the efficacy and safety profile of this vaccine candidate."

Takeda's product is the second dengue vaccine to come to market, after Sanofi Pasteur's Dengvaxia. Sanofi's vaccine was 56% to 61% efficacious in preventing virologically confirmed dengue among children, but it was tied to severe illness in dengue-naive children who received the vaccine and subsequently contracted the virus. It is as yet unknown if Takeda's vaccine will elicit a similar response in dengue-naive recipients.
Nov 6 N Engl J Med study


Study: Antibiotic prophylaxis after cardiac arrest cuts pneumonia risk

A short course of antibiotics for patients receiving targeted temperature management after cardiac arrest reduced incidence of early ventilator-associated pneumonia (VAP), French researchers reported today in the New England Journal of Medicine.

In a randomized, placebo-controlled trial conducted in 16 French intensive care units (ICUs), researchers set to determine whether 2 days of empirical, prophylactic antibiotic therapy could prevent early VAP in patients who were being ventilated after out-of-hospital cardiac arrest related to initial shockable rhythm and treated with targeted temperature management (at 32ºC to 34ºC)—a strategy associated with increased risk of secondary infections.

 A total of 198 adults were enrolled in the study and randomized to receive 2 days of intravenous amoxicillin-clavulanate or placebo. The primary outcome was VAP during the first 7 days of hospitalization; secondary outcomes included late incidence of VAP, length of ICU stay, number of ventilator-free days, mortality at day 28, and intestinal acquisition of multidrug-resistant bacteria at day 7.

A total of 60 cases of VAP were confirmed, including 51 early cases. The incidence of early VAP was lower with antibiotic prophylaxis than with placebo (19 patients [19%) vs 32 patients [34%]; hazard ratio, 0.53; 95% confidence interval [CI], 0.31 to 0.92; P = 0.03). But no significant differences were observed between the antibiotic and placebo groups for incidence of late VAP (4% and 5%, respectively), number of ventilator-free days (21 days and 19 days), ICU length of stay (5 days and 8 days), and mortality at day 28 (41% and 37%). No increase in resistant bacteria was identified in the antibiotic group, and serious adverse events did not differ significantly between the two groups.

The authors of the study note that patients with overt respiration were not included in the study, and that systematic implementation of bundles known to decrease the incidence of VAP in the ICU was highly recommended. In addition, more than one fourth of the VAP cases initially reported by investigators were not confirmed by independent adjudication committee, resulting in lower incidence of VAP compared with previous trials.
Nov 7 N Engl J Med abstract


Salt-cured fish implicated in 2 New Jersey botulism cases

A New Jersey woman and her adult daughter were diagnosed as having botulism type E last fall after eating an Egyptian salt-cured fish dish called fesikh, health officials from New Jersey and the US Centers for Disease Control and Prevention (CDC) reported today in Morbidity and Mortality Weekly Report (MMWR).

The 55-year-old mother and her 30-year-old daughter arrived at the emergency department at the same time 16 hours after symptoms began, which included abdominal pain, vomiting, and diarrhea. The daughter also had other symptoms, such as blurry vision and difficulty breathing.

Two days earlier, both women had consumed fesikh, made by the mother with mullets bought frozen at a local Asian market. She salt-ured and fermented the uneviscerated fish, which involved keeping it in plastic for 20 days at room temperature.

The medical team suspected botulism because of the patients' exposure to fesikh and the symptoms they had. After consulting with the CDC, the agency released heptavalent botulism antitoxin, which was administered to both women. They both survived after 2 days in the ICU and 7 days in the hospital.

The authors wrote that the case highlights the importance of early recognition and treatment and the role of salt-cured fish dishes as a potential botulism vehicle.
Nov 8 MMWR note from the field


Report shows wide range of flu vaccine protection in Southern Hemisphere

A comparison of 2019 flu season patterns and early estimate of flu vaccine effectiveness (VE) in four Southern Hemisphere countries found that flu activity timing and dominant flu strains varied, as did VE. Researchers from the four countries—Australia, Chile, New Zealand, and South Africa—reported their findings today in Eurosurveillance.

Overall, early flu VE estimates were highest for 2009 H1N1 and lowest for H3N2. For example, all-ages VE estimates for 2009 H1N1 ranged from 7% to 70%, for H3N2, 4% to 57%, and for influenza B, 29% to 66%.

The authors warned that the usefulness of the findings for the Northern Hemisphere may be limited, because the Southern Hemisphere vaccine shares only one of four components with the Northern Hemisphere's 2019-20 vaccine. However, they note that World Health Organization (WHO) vaccine advisors considered the vaccine performance when they met in September to recommend strains for the Southern Hemisphere's 2020 flu season.

They note that the estimates are expected to vary based, for example, on small sample sizes, different definitions of severe acute respiratory infection, and different vaccine formulations used in each country.
Nov 7 Eurosurveill report


WHO taps Johns Hopkins center as collaborator for global health security

The WHO has named the Johns Hopkins Center for Health Security as a collaborating center for global health security, a designation that will allow Johns Hopkins University (JHU) to carry out activities and research to support WHO programs.

"Our Center has worked closely with WHO over the past few years, supporting a variety of their activities in the field of global health security. We admire WHO's commitment to strengthening global health security, and we look forward to furthering our work with them in this important area," said Tom Inglesby, MD, director of the Johns Hopkins Center for Health Security, in a press release.

As a collaborating center, the school will support various WHO-led global health efforts, including assessing natural and deliberate threats to global health security, supporting global health technology, and providing research on global health topics.

JHU is the seventh collaborating center to work with the WHO.
Nov 6 JHU press release

This week's top reads

Our underwriters