CRISPR-based phage therapy shows promise in first human trial

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Danish microbiome technology company SNIPR Biome today announced positive results from a phase 1 study of their CRISPR-based phage therapy targeting Escherichia coli in the gastrointestinal tract.

SNIPR001 contains four bacteriophages (bacteria-killing viruses) armed with CRISPR/Cas DNA editing technology designed to selectively eradicate E coli in the gut, including antibiotic-resistant strains. Interim results from the 36-person phase 1 trial, which aimed to examine the safety profile and pharmacodynamics of SNIPR001, showed that oral dosing over 7 days was well tolerated, with only mild to moderate side effects. In addition, treatment with SNIPR001 numerically lowered gut E coli levels.

Bacteriophage
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The treatment will initially be targeted at patients with hematologic cancers (like lymphoma and leukemia) who are undergoing hematopoietic stem-cell transplants and are vulnerable to bloodstream infections that occur when E coli translocates from the gut into the blood. The most common antibiotic treatment, fluoroquinolones, are ineffective against fluoroquinolone-resistant E coli strains and tend to damage the gut microbiome by wiping out beneficial bacteria.

Company officials say the findings demonstrate clinical proof of principle for the new technology.

"With the combined killing effects of bacteriophages and CRISPR-Cas technology, SNIPR001 has demonstrated the ability to target and eliminate antibiotic-resistant E. coli strains in the gut, providing a safe alternative to traditional treatments that do not work against antibiotic-resistant strains, while sparing the rest of the gut microbiome," SNIPR Biome co-founder and CEO Christian Grondahl, PhD, DVM, said in a press release.

"This is a significant milestone in our mission to develop groundbreaking solutions in the fight against antimicrobial resistance, and we look forward to advancing SNIPR001 through further clinical studies to learn more and ultimately, we hope, to improve patient outcomes," he added.

Future trials will investigate whether SNIPR001 reduces the rate of E coli bloodstream infections in cancer patients.

SNIPR Biome received $3.9 million in funding in May 2021 from CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator) to develop SNIPR001.

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Analysis: Mother-to-newborn COVID-19 transmission infrequent

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A meta-analysis of 26 studies involving mother-to-child COVID-19 transmission in the first 30 days after birth reveals an overall estimate of SARS-CoV-2 infection among infants of 2.3%. The study was published today in Scientific Reports.

During the initial months of the COVID pandemic, many hospitals stopped practices known to promote breastfeeding and maternal bonding when the mother had an active COVID-19 infection at delivery, including infant room-in, skin-to-skin contact, and breastfeeding itself.Mom and baby

Subsequent studies have shown breastmilk is unlikely to transmit COVID-19 to infants, and indeed contains neutralizing antibodies when mothers have an active infection.

Low risk with close contact after birth

The current study was based on outcomes seen among of 2,653 mothers with SARS-CoV-2 and 2,677 infants included in the 26 studies, all based in high-income countries. The risk of infection was similar for mothers who had newborns room-in with them at the hospital, and among newborns who went to a nursery following birth.

The overall estimate of SARS-CoV-2 infection among infants was 2.3% (95% confidence interval [CI], 1.4% to 3.2%). Data from studies with (1.4%; 95% CI, 0.8% to 2.0%) and without (1.3%; 95% CI, 0.0% to 2.7%) rooming-in provided similar risk of infection, the authors said.

"Mother-to-child transmission in the neonatal period appears to be relatively low and consistent with previously published data," the authors concluded. "Our data support that the balance between the potential risk of postnatal transmission of the virus by the mother is decisively outweighed by the well-known benefits of skin-to-skin contact, rooming-in practice and above all, breastfeeding."

France reports rise in severe neonatal infections from enterovirus variant

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French health officials have reported an unusual rise in neonatal sepsis cases that has led to seven deaths and involves enterovirus (echovirus-11 [E-11]), the World Health Organization (WHO) said today in an outbreak notice.

Between July 2022 and April 2023, nine cases were reported from four hospitals in three regions, all involving hepatic involvement and multiorgan failure. Seven babies died, and two are still hospitalized. The cases are linked to a recombinant E-11 lineage that hasn't been detected in France before and is considered unusual due to extremely rapid health deterioration and a high case-fatality rate. Though severe E-11 has occurred before in twins, the proportion in the current group is higher than expected.ICU baby

Eight of the babies were preterm, and there were four pairs of twins among the total group. All experienced clinical signs from 1 to 7 days after birth, hinting at mother-to-child transmission. Tests confirmed maternal infection with E-11 in four of the five mothers, and the ones who tested positive had experienced gastrointestinal symptoms or fever within 3 days of delivery.

Data from 2016 through 2021 found the proportion of severe neonatal infections from E-11 rose from 6.2% over the time period to 55% in 2022.

The WHO said the risk to the general population is low, despite the worrisome increase. It urged clinicians treating newborns and young infants for circulatory shock to consider sepsis and conduct diagnostic tests, including for enterovirus.

Wisconsin, Texas report more CWD cases in deer

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Chronic wasting disease (CWD) has been detected on another Wisconsin deer farm and for the first time in Bexar County, Texas.

The Wisconsin Department of Agriculture, Trade and Consumer Protection (DATCP) yesterday confirmed CWD in a 10-year-old doe on a 22-acre deer farm in Sauk County. The National Veterinary Services Laboratories (NVSL) in Ames, Iowa, confirmed the case. The farm remains under quarantine as veterinarians from the DATCP and the US Department of Agriculture conduct an epidemiologic investigation.

The Texas Parks and Wildlife Department (TPWD) yesterday announced that a free-range white-tailed deer in Hollywood Park, Bexar County, has tested positive for CWD. The deer was harvested as part of a deer population-control effort in late January. The NVSL confirmed the case.

TPWD said it will hold community meetings this summer on mitigation actions and CWD zone establishment. The disease was first detected in Texas in 2012.

CWD is a fatal neurodegenerative disease caused by infectious prions (misfolded proteins) that affects cervids such as deer, elk, and moose. In addition to North America, the infection has been identified in several Nordic countries and South Korea. While the disease is not yet known to affect humans, the US Centers for Disease Control and Prevention and the World Health Organization recommend against consuming meat from CWD-infected cervids.

Bangladeshi study finds high levels of multidrug-resistant, foodborne Salmonella

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A systematic review and meta-analysis found significant levels of multidrug-resistant Salmonella in livestock- and poultry-derived foods in Bangladesh, researchers reported today in JAC-Antimicrobial Resistance.

The 12 studies included in the meta-analysis were published from 2000 to 2022 and examined 1,411 food samples derived from chickens, cattle, and goats. The combined prevalence of Salmonella in the samples was 37%, and subgroup analysis found a high prevalence of resistance to routinely used antibiotics among the Salmonella isolates, including tetracycline (81%), oxytetracycline (52%), doxycycline (51%), sulfamethoxazole/trimethoprim (42%), and ciprofloxacin (20%). A univariate meta-analysis and correlation analysis found that the prevalence of Salmonella increased with every year.

The World Health Organization estimates that Salmonella causes 93.8 million cases of gastroenteritis globally. In addition to the threat posed to people consuming Salmonella-contaminated food, the study authors note that the findings are particularly concerning in a country like Bangladesh, where domestic chickens—the most common source of Salmonellosis—are routinely given antibiotics, live close to humans, and can shed the bacteria into the environment.

"AMR [antimicrobial resistance] is expected to increase by 70% in Asia, posing a national and global threat," they wrote. "To reduce the risk of pathogenic AMR bacteria originating from animal origin foods, raising awareness about the rational use of antibiotics in food animals, safe food handling and safe cooking practices is obligatory."

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