British drugmaker GSK announced yesterday that its investigational tuberculosis (TB) drug produced positive results in a phase 2a study.

GSK said the results of the single-center, open-label trial showed that GSK3036656, a first-in-class antitubercular agent that suppresses protein synthesis in Mycobacterium tuberculosis, demonstrated early bactericidal activity and was well tolerated after 14 days in patients with drug-sensitive pulmonary TB. The trial involved four cohorts of 12 to 20 patients who were randomized to receive 1, 5, 15, or 30 milligrams (mg) of GSK3036656 or the standard-of-care drug.

Anti-mycobacterial activity for doses of 5 to 30 mg was demonstrated in terms of reducing the number of viable TB cells and an increase in the time to detect bacterial growth in culture. Positron emission tomography also showed a reduction in TB disease in participants who received 30 mg.

Company officials say the findings suggest GSK3036656 could be part of a shorter and simpler TB treatment regimen.

"Existing treatments for TB can be complicated, of long duration and have serious side effects which significantly impact the lives of patients with TB around the world," David Barros-Aguirre, PhD, GSK's Head of Global Health Medicines R&D, said in a company press release. "Today's encouraging data provide a good foundation from which to investigate GSK3036656 in different combinations in Phase IIb/c studies, with the aim of contributing to shorter, simpler and better tolerated treatment regimens for patients with TB."

US adults who get vaccinated against the flu every year were 24.7% more likely to complete a primary COVID-19 vaccine regimen than those who never received the flu vaccine, finds a study yesterday in JAMA Network Open.

Rand Corp. researchers used their American Life Panel, a probability sample of US adults, to analyze self-reported flu vaccine uptake in the 2009 to 2017, 2019-20 (largely prepandemic), and 2021-22 (pandemic) flu seasons. The team also evaluated COVID-19 vaccine status during the latter two seasons.

Of 1,366 survey respondents, 85% were White, 11% were Hispanic, 7% were Black, and 2% were Asian. Average age was 56 years.

Among 358 participants who always received the flu vaccine through 2017, 81.4% to 92.2% still did so two to four seasons later. But of 642 respondents who never received the flu vaccine, only 20.3% received it in 2019 to 2020, rising to 23.5% during the pandemic. Those who always got the flu shot were 24.7% more likely to be vaccinated against COVID-19 than those who never did so.

COVID-19 vaccination was 50% more common in respondents vaccinated against the flu in 2021-22 (90.8% of 944 vs 60.9% of 723; risk ratio [RR], 1.50). And flu vaccine uptake in 2021-22 was 230% higher among COVID-vaccinated participants (57.1% of 1,025 vs 17.3% of 341; RR, 3.30).

COVID-19 vaccinees were much more likely to receive the flu vaccine in 2022 after not receiving it in 2020 (odds ratio [OR], 12.82). Recipients of both vaccines had higher educational attainment, while Democrats were more likely than Republicans to receive the COVID-19 vaccine (OR, 4.43) but not to switch from not receiving to receiving the flu vaccine.

"Most strikingly, among individuals who historically never got the influenza vaccine, those receiving COVID-19 vaccine were substantially more likely to switch toward getting the influenza vaccine," the authors wrote. "This suggests that investing in vaccine acceptance has payoffs beyond the vaccine itself."

A non-peer-reviewed retrospective cohort study of 2,126 Jynneos monkeypox vaccine recipients identified 10 cardiac events that all had alternative explanations, and no hospitalizations or serious adverse outcomes were attributed to vaccination.

The study, published on the preprint site medRxiv, aimed to document any cardiac events after Jynneos vaccination, as the Advisory Committee on Immunization Practices (ACIP) stated that people with underlying heart disease or three or more major cardiac risk factors should be counseled about the theoretical risk for myopericarditis following vaccination with Jynneos.

The authors used vaccine recipients in the Kaiser Permanente Northwest system who were vaccinated with at least one dose of Jynneos between Jul 14 and Oct 10, 2022. The authors found there were 10 confirmed cardiac events for an incidence of 3.1 per 1000 doses given with (exact 95% confidence interval [CI] 1.5 to 5.7).

"Of these 10 events, none could be attributed directly to the vaccination," concluded the authors, who worked with a team of physicians to review events and outcomes.

"This initial study provides timely information for the clinician counseling their patient with underlying cardiac risk factors on the low observed risk of cardiac events with Jynneos vaccination during the 2022 monkeypox public health emergency."

Uganda has reported one more lab-confirmed Ebola infection, which involves a 23-year-old woman who is a healthcare worker in Mubende, one of the outbreak's hot spots, according to an update yesterday from the World Health Organization (WHO) Uganda office.

Her illness lifts Uganda's Ebola total to 140 cases and the number of infected health workers to 19, including 7 who died from their infections.

No new deaths were reported, keeping fatalities at 55. The case-fatality rate among the confirmed cases is 39%. Uganda has also reported at least 21 suspected cases, mostly from earlier in the outbreak, all of which were fatal.

Uganda's outbreak began in September and involves the more rare Sudan Ebola strain. Unlike the more common Zaire Ebola strain, there are no approved treatments or vaccines. Officials have said a small number of patients have received experimental treatments, and plans are under way to test as three vaccine candidates.

Flu activity in the Northern Hemisphere is rising, with levels up sharply over the past few weeks in North America, the World Health Organization (WHO) said yesterday in its latest global flu update, which roughly covers the last half of October.

The WHO's update also covered other respiratory infections, including respiratory syncytial virus (RSV), which is on the rise in several parts of the world.

In the United States and Canada, flu activity was above national baselines for this time of year, with the H3N2 strain predominant. Both countries are experiencing increased RSV activity. Europe's flu activity is also rising, especially in Germany, Portugal, and Spain, but is still considered low.

Other areas seeing rises include Kazakhstan in central Asia, plus some countries on the Arabian Peninsula. Flu increased sharply in southern Asia, led by brisk activity in Iran.

Some of South America's temperate countries reported rising flu markers, including Argentina, Chile, and Uruguay.

Other countries with available information reporting rises in RSV illness include France, Ireland, South Korea, and Brazil.

Of respiratory samples testing positive for flu at national labs during the latter part of October, 92.8% were influenza A. Of the subtyped flu A samples, 78.8% were H3N2. Of the subtyped influenza B samples, all belonged to the Victoria lineage.

Child's death from flu, RSV in California

In a related development, the California Department of Public Health (CDPH) yesterday reported the first death of the winter season from flu and RSV in a child younger than 5. It said young children are most vulnerable to severe complications from RSV in flu, especially if they have underlying health conditions or were born premature.

Because of patient confidentiality, the CDPH did not release any other details about the case.

Owing to a further rise in hospitalizations from an early winter virus season, the CDPH also issued new guidance for responding to a surge of infections in pediatric patients, which allows hospitals to reconfigure space to accommodate the surge.

The CDPH also recommended that inpatient and outpatient facilities without existing pediatric services explore short-term measures to expand capacity for treating pediatric patients.

Italian investigators conclude that the relative vaccine effectiveness (RVE) of a second booster vaccine dose against severe COVID-19 is only about 30% after 2 to 4 months in people 80 and older compared with protection after the first booster dose. The study is published in Vaccine.

The RVE of the second booster dose was negligible for general infections at 2 to 4 months for those 80 and older. The study was conducted between April and August of 2022, during a time of Omicron BA.2 and BA.5 subvariant dominance.

To conduct the study, researchers matched data from the national vaccination registry and the COVID-19 surveillance system in a 1:1 ratio of individuals who received the second booster vaccine dose with individuals who received the first booster vaccine dose at least 120 days earlier. A total of 831,555 matched pairs were analyzed.

A second booster dose of mRNA vaccine, 14 to118 days post administration, was moderately effective in preventing SARS-CoV-2 infection compared to a first booster dose administered at least 120 days earlier (14.3%, 95% confidence interval [CI]: 2.2-20.2), the authors said.

Overall RVE decreased from 28.5% (95% CI: 24.7-32.1) in the time-interval 14 to 28 days to 7.6% (95% CI: -14.1 to 18.3) in the time-interval 56 to118 days. For severe COVID, there was more protection, decreasing from 43.2% (95% CI: 30.6-54.9) to 27.2% (95% CI: 8.3-42.9) over the same time span.

"Although RVE against SARS-CoV-2 infection was much reduced 2-4 months after a 2nd booster dose, RVE against severe COVID-19 was about 30%, even during prevalent circulation of the Omicron BA.5 subvariant," the authors concluded.