News Scan for Jul 15, 2021

News brief

Shorter regimen for resistant TB found effective with lower linezolid dose

New data presented today indicate that a shorter treatment regimen for highly drug-resistant forms of tuberculosis (TB) remains highly effective with reduced doses of one of its components.

The phase 3 ZeNix trial, conducted in Moldova, Georgia, Russia, and South Africa, assigned 181 patients with extensively drug-resistant (XDR)-TB, pre-XDR-TB, and failed or treatment-intolerant multidrug-resistant TB into four study arms. The patients were all treated with the BPaL (bedaquiline, pretomanid, and linezolid) regimen for 6 months, with each arm receiving a different dose of linezolid.

A previous trial, the Nix-TB trial, had found that treatment efficacy for the BPaL regimen was 89%, but with high rates of side effects, such as peripheral neuropathy and anemia, that were associated with linezolid.

Per the intent-to-treat analysis, the treatment success rate was 93% for patients who received the highest dose of linezolid (1,200 milligrams [mg] for 6 months), and was similarly high in the remaining arms—89% among patients receiving 1,200 mg for 2 months, 91% for those receiving 600 mg for 6 months, and 84% among those who treated with 600 mg for 2 months.

Reported side effects also declined with lower doses of linezolid. Peripheral neuropathy was reported in 38% of those receiving the highest dose, compared with 13% of those receiving the lowest dose. A similar downward trend in patients reporting anemia was observed.

"The results of the ZeNix trial support the observed high efficacy of the BPaL regimen as seen in the Nix trial," principal trial investigator Francesca Conradie, MD, said at a press conference ahead of the International AIDS Society conference, where the results will be presented. "There appears to be a lower dose of adverse events of note, with a preservation of the high rate of efficacy of around 90%."

The BPaL regimen was approved for use in patients with highly resistant TB in 2019. The 6-month, all-oral regimen is significantly shorter and more effective than previous treatment regimens, which lasted at least 18 months and had global success rates of only 43%.

"We now have evidence that the BPaL regimen can be optimized to make it even easier to use," Mel Spigelman, MD, President and CEO of TB Alliance, which developed pretomanid for use in the regimen, said in a press release.
Jul 15 TB Alliance press release

CDC notes seasonal rise in Cyclospora cases: 208 cases in 22 states

In a regular update on domestically acquired Cyclospora cases, which typically rise in the spring and summer, the US Centers for Disease Control and Prevention (CDC) yesterday said 208 cases have been reported in 22 states and New York City.

So far, no food items have been linked to the illnesses, but cyclosporiasis in the past has been associated with fresh produce including basil, cilantro, mesclun lettuce, raspberries, and snow peas. Earlier cases have been linked to outbreaks, such as a bagged salad event in 2020, but often cases aren't directly linked to outbreaks, because there is no validated genetic fingerprinting method for Cyclospora.

The latest total reflects an increase of 202 cases since the CDC's last update in June. So far 21 patients were hospitalized, and no deaths have been reported.

For comparison, in 2020, multiple outbreaks and clusters were detected involving different produce items, including bagged salad. From May through September, the CDC reported 1,241 cases in 34 states and New York City.

The infections are caused by a parasite called Cyclospora cayetanensis, which is spread by eating food or drinking water contaminated with feces. The hallmark of the illness is profuse diarrhea that can last weeks to months.
Jul 14 CDC Cyclospora update

COVID-19 Scan for Jul 15, 2021

News brief

Early monoclonal antibody combo for COVID-19 cuts hospital, death rates

Yesterday in the New England Journal of Medicine results from a phase 3 trial showed that a combination of bamlanivimab plus etesevimab monoclonal antibodies led to a lower incidence of COVID-19–related hospitalization and deaths.

The therapy also accelerated the decline in the SARS-CoV-2 viral load in patients who received the treatment, if administered within 3 days of diagnosis of mild to moderate COVID-19 in patients with at least one risk factor for developing serious disease.

The trial including 1,095 patients who either received a single intravenous infusion of either a neutralizing monoclonal-antibody combination agent (2,800 milligrams [mg] of bamlanivimab and 2,800 mg of etesevimab, administered together) or placebo within 3 days after a laboratory diagnosis of SARS-CoV-2 infection, the authors said.

By day 29 after infusion, 11 of 518 patients (2.1%) in the bamlanivimab-etesevimab group had a COVID-19–related hospitalization or death as compared with 36 of 517 patients (7.0%) in the placebo group (absolute risk difference, −4.8 percentage points; 95% confidence interval [CI], −7.4 to −2.3; relative risk difference, 70%; P < 0.001).

No deaths occurred in the monoclonal antibody group. In the placebo group, 10 deaths occurred, 9 of which were designated as caused by COVID-19.

"These results provide support for the potential of neutralizing monoclonal-antibody therapy to reduce both the risk of progression to severe disease and the severity of disease among high-risk patients with symptomatic Covid-19," the authors concluded.

In an editorial audio interview, editors of the journal said though the results are positive, the use of the antibodies in a single intravenous infusion had limited real-world application for outpatients. And determining day 3 or 4 of infection was a difficult task with a virus that presents so differently across the patient population.
Jul 14 N Engl J Med study
Jul 14 N Engl J Med editorial

Learning disabilities tied to higher risk of COVID-19 hospitalization, death

Adults with learning disabilities who were diagnosed as having COVID-19 were five times more likely to be hospitalized and eight times more likely to die during England's first COVID wave, according to a study in BMJ. The researchers noted that data from the second wave (September 2020 to early February 2021) showed similar results.

During the first COVID-19 wave, which ran from Mar 1 to Aug 31, 2020, the researchers looked at electronic health records for 14,312,023 adults 16 and older, of whom 90,307 (0.63%) were in the national learning disability register. Of this subgroup, 0.6% (538) were hospitalized for COVID and 0.25% (222) died from the disease, compared with 0.2% (29,781) of adults not on the registry who were hospitalized for COVID and 0.1% (13,737) who died from it. The adjusted hazard ratio for COVID hospitalization was 5.3 (95% confidence interval [CI], 4.9 to 5.8); for COVID-related death, it was 9.2 (95% CI, 7.2 to 9.4).

The researchers also found increased associated COVID-19 risks for children with learning disabilities (albeit in small absolute numbers) as well as adults with Down syndrome or cerebral palsy.

Adults on the register were more likely to be male, be younger, live in more deprived areas, and have diabetes, obesity, other neurologic disease, or a serious mental illness. About 82% were considered to have mild to moderate learning disability.

"We must work much harder to reduce the health inequalities exposed and amplified by the pandemic—including further training of all health and care staff about the needs of people with learning disabilities and the health inequalities they face," write Ken Courtenay, MB BCh, and Vivien Cooper, CEO of the Challenging Behaviour Foundation, in a commentary that highlighted concerning no-resuscitation orders and the need for better vaccination priority.

"People with learning disabilities have the same rights as everyone else, including the right to good health and to be safe from harm."
Jul 15 BMJ study and commentary