In the wake of brisk rainfall since June, Bangladesh is experiencing a large dengue outbreak that is unusual in its scale and seasonality, the World Health Organization (WHO) said yesterday in an outbreak notice. The group added that high temperatures and high humidity, alongside the heavy rainfall, have increased mosquito populations throughout Bangladesh, where dengue is endemic.

The WHO said the outbreak is the country's second largest since 2000, second only to a large event in 2019. As of Nov 20, the health ministry has reported 52,807 lab-confirmed cases, plus 230 related deaths, for a case fatality rate of 0.44%. The predominant serotypes are dengue virus 3, predominant since 2019, and dengue virus 4, which hadn't been reported in the country for several years.

Though all eight of Bangladesh's divisions have reported cases and deaths, the most affected one is Dhaka, which has reported 70.6% of cases and 60.4% of deaths. Much of the activity has been from the city of Dhaka, the country's largest city.

The WHO said Bangladesh's climate conditions are becoming more favorable to the transmission of dengue and other vector-borne diseases. It said factors include excessive rainfall, waterlogging, flooding, a rise in temperature, and unusual shifts in the country's traditional seasons. The WHO said Bangladesh experienced moderate rainfall in October, which is outside of the monsoon season that typically runs from May to September.

The WHO also said Bangladesh has repurposed six hospitals dedicated for COVID-19 in the city of Dhaka for managing dengue cases. Among other response efforts, the ministry and WHO have distributed 284,000 diagnostic kits to hospitals throughout the country.

Adapting COVID-19 standards of care (SOC) to evolving information about optimal treatments may have shortened recovery and reduced deaths in hospitalized adults during some pandemic phases, according to an observational study today in the Annals of Internal Medicine.

A team led by researchers from the US National Institute of Allergy and Infectious Diseases analyzed data from the Adaptive COVID-19 Treatment Trial (ACTT), a staged, phase 3, randomized, controlled trial that assessed 28-day recovery and mortality from February 2020 to May 2021. The trial was conducted in 94 hospitals in 10 countries, with roughly 500 patients per group and 86% of participants from the United States.

ACTT-1 compared the antiviral remdesivir plus SOC to placebo plus SOC, while remdesivir plus SOC was the control group in ACTT-2 and ACTT-3. In ACTT-3 and ACTT-4, the analysis was repeated for participants who received remdesivir plus the anti-inflammatory dexamethasone plus SOC. ACTT-4 compared remdesivir plus the immune inhibitor baricitinib to remdesivir plus dexamethasone.

Outcomes were marginally improved in ACTT-2 over ACTT-1 (adjusted hazard ratio [aHR] for recovery, 1.04; aHR for death, 0.90). Patients were less likely to be intubated in ACTT-2 than in ACTT-1 (odds ratio, 0.75), and hydroxychloroquine use fell.

Outcomes improved from ACTT-2 to ACTT-3 (aHR for recovery, 1.43; aHR for death, 0.45). Explanations for the differences, including changing case loads, SOC, and SARS-CoV-2 variants, were comparable in ACTT-2 and ACTT-3, except for greater dexamethasone use (11% to 77%). ACTT-3 and ACTT-4 outcomes were similar. Across all stages, antibiotic use decreased.

"Although our unadjusted HR estimates describe differences in outcomes between trial stages, the propensity score-weighted HRs account for changes in patient composition over time and represent a 'stage effect' attributed to the SOC received during different stages," they wrote.

The authors noted that they found no improvements in recovery or mortality from August 2020 to May 2021, perhaps because the SOC didn't change much during that time. "These findings support the exclusion of nonconcurrent controls when analyzing data from platform trials, particularly for COVID-19 treatments and vaccines," they concluded.

An analysis of outpatient antibiotic prescriptions from primary healthcare facilities (PHFs) in six Chinese provinces found that more than 70% were inappropriate, Chinese researchers reported last week in Clinical Microbiology and Infection.

In the nationwide survey of outpatient antibiotic prescriptions ordered from Chinese primary care facilities, researchers at Peking University collected data on all outpatient-visit prescriptions from 269 Chinese PHFs in 31 cities in six provinces from 2017 to 2019. They randomly selected 100 outpatient antibiotic prescriptions from each facility, then classified them as appropriate, potentially appropriate, and inappropriate based on the diagnosis for which they were prescribed. They also analyzed the type of antibiotics prescribed and the costs associated with inappropriate prescribing.

Of the 641,732 prescriptions analyzed, 209,662 (32.7%) included at least one antibiotic. Of those antibiotic prescriptions, 4.8% were classified as appropriate, 20.6% as potentially appropriate, and 70.5% as inappropriate. Upper respiratory tract infections, acute bronchitis, and non-infectious gastroenteritis were responsible for 68.9% of inappropriately antibiotic prescriptions. A total of 256,474 individual antibiotics were prescribed, of which 82.2% were broad-spectrum antibiotics, with second-generation cephalosporins (15.1%) and third-generation cephalosporins (14.6%) being the most commonly prescribed subgroups.

Higher inappropriate antibiotic prescribing rates were observed in children aged 0 to 5 years (78.5%) and patients living in economically undeveloped areas (77.5%). Cumulative spending on inappropriate antibiotics accounted for 66.8% of the total cost of antibiotics.

The study authors say antibiotic stewardship efforts should target certain conditions (i.e., upper respiratory tract infections, acute bronchitis, and non-infectious gastroenteritis) and on clinicians and children in cities of lower economic status.

"Real-world evidence is increasingly appreciated as fundamental to the development of antibiotic stewardship and interventions aiming at modifying antibiotic prescribing and improving patients' health," they wrote. "Tailored training and continuous education for primary clinicians that promote accurate diagnosis and evidence-based treatment based on clinical guidelines are urgently needed."

Today in Annals of Internal Medicine, researchers show that, compared to 2020, mortality rates due to COVID-19 infections among young adults increased significantly in 2021, suggesting younger people had lower vaccine uptake and adhered to fewer COVID precautions than older adults in the United States

To understand the age shift that occurred among COVID-19 deaths in the United States, researchers used Years of Life Lost (YLL) rather than mortality during March to December of 2020 and March to December of 2021. The study was based on data from the CDC WONDER (Centers for Disease Control and Prevention Wide-ranging ONline Data for Epidemiologic Research), with life expectancies based on the World Health Organization global health estimate from 2017.

During those two periods, the median age of COVID-19 deaths decreased from 78 years in 2020 to 69 years in 2021, and YLL due to COVID-19 increased to 7.4% more years of life lost in the second pandemic year due to a 35.7% increase in YLL per COVID-19 death. Despite those changes, there were 20.8% less COVID-19 deaths in 2021 versus 2020.

"Further investigation should determine the extent to which this downward age shift in COVID-19 mortality is attributable to high early-pandemic COVID-19 death rates among older adults (for example, involving nursing homes and long-term care facilities), relatively higher vaccine coverage and adherence with nonpharmaceutical interventions among older versus younger adults later in the pandemic, age-related risk differences associated with coronavirus variant viruses, or other mechanisms," the authors said.

The analysis showed other changes to YLL during 2020 to 2021: YLL and deaths due to unintentional injuries increased considerably, owing in part to record-high drug overdose deaths, up 15% (nearly 14,000 deaths) in 2021 compared with 2020, the authors said.

"A shift in COVID-19 mortality to relatively younger people in the second pandemic year contributed to markedly increased premature mortality from this increasingly preventable death," said corresponding author Mark Czeisler, PhD, medical student at Harvard Medical School, in a press release. "Understanding the factors that contribute to this age shift is critical as we continue developing our knowledge of the COVID-19 pandemic."

Six states reported more highly pathogenic avian flu outbreaks in poultry flocks over the past few days, including three that reported large losses in commercial poultry, according to updates from the US Department of Agriculture (USDA) Animal and Plant Health Inspection Service (APHIS).

Last week, the mounting poultry losses matched the record of 50.5 million set during multistate outbreaks in 2015. Outbreaks reported over the past few days boosted the national total for the year to 52.5 million from 46 states.

In one of the newly reported outbreaks, the virus struck a large layer farm in Nebraska's Dixon County that houses 1.7 million birds. Also, South Dakota reported four more outbreaks from commercial turkey farms in three counties (Beadle, Spink, and Faulk) which taken together had more than 222,000 birds. Also, Minnesota reported another outbreak at a turkey farm, this time at a facility in Todd County that had 44,500 birds.

Four states reported more outbreaks in backyard flocks, including Alaska, South Dakota, Florida, and Oregon.

First high-path outbreak in Ecuador

In international developments, Ecuador reported its first highly pathogenic avian flu outbreak in poultry, likely part of a recent incursion of the Eurasian H5N1 strain into South America. The virus is awaiting full subtyping.

The outbreak occurred at a layer farm near the city of Latacunga in north-central Ecuador that had experienced unusual morality, according to a notification from the World Organization for Animal Health (WOAH). The virus killed 49,900 of 180,100 birds.

The development comes in the wake of recent H5N1 detections in South American birds, including events in Peru and Colombia.