Uganda receives first Ebola vaccine trial doses

News brief

Uganda's health ministry today announced that the country has received 1,200 doses of a candidate Sudan Ebola vaccine from the World Health Organization (WHO) Uganda office, which is slated for use in a clinical trial.

The WHO's African regional office said the doses arrived just 79 days after the outbreak was declared and that the clinical trial will be conducted by a team from the University of Makerere, with support from the health ministry and the WHO. Currently, there are no licensed vaccines or treatments for the Sudan Ebola strain.

The doses are from the Sabin Vaccine Institute (SVI), according to Reuters. The SVI vaccine is a modified chimpanzee adenovirus (ChAd3) vector vaccine. Health officials had earlier cleared plans to study three candidate Ebola Sudan vaccines. The others are from Merck and Oxford University.

In the middle of November, a WHO working group recommended that ring vaccine trials prioritize the VSV-EBOV vaccine candidate licensed by International AIDS Vaccine Initiative (IAVI) candidate, owing to the safety and efficacy of the VSV-EBOV platform used for the Zaire Ebola vaccine, followed by the SVI vaccine, then the Oxford vaccine. IAVI licensed the vaccine from Merck, which donated doses it had already made, and is advancing the development of the Sudan VSV-EBOV vaccine.

A sharp decline in Uganda's Ebola cases presents an obstacle to ring vaccination trials. The last patient was discharged from treatment more than a week ago, and Uganda's 42-day countdown, covering two incubation periods, toward the end of the outbreak has begun.

(Editorial note: This news brief includes clarifications made on Dec 9 to more accurately describe IAVI's licensing and development of the Sudan Ebola VSV-EBOV vaccine.)

Antivirals—not monoclonal antibodies—neutralize Omicron BQ.1.1, XBB

News brief

The Omicron BQ.1.1 and XBB SARS-CoV-2 subvariants evade the monoclonal antibodies imdevimab, casirivimab, tixagevimab, cilgavimab, bebtelovimab, and S309—but not the antiviral drugs remdesivir, molnupiravir, and nirmatrelvir (Paxlovid), according to a research letter published yesterday in the New England Journal of Medicine.

A team led by University of Tokyo researchers used a live-virus neutralization assay to test the efficacy of the monoclonal antibodies and antivirals against BQ.1.1 and XBB isolated from infected patients.

Imdevimab, casirivimab, tixagevimab, cilgavimab, and S309 (precursor of sotrovimab) didn't neutralize BQ.1.1 or XBB, even at the highest concentrations tested. Bebtelovimab, which neutralizes Omicron BA.1, BA.2, BA.4, and BA.5, had no efficacy against BQ.1.1 or XBB. Neither combination of antibodies tested (imdevimab-casirivimab and tixagevimab-cilgavimab) neutralized BQ.1.1 or XBB.

Because they are no match against the newer Omicron subvariants, the only monoclonal antibody medication still authorized by the US Food and Drug Administration (FDA) to lower the risk of COVID-19 is tixagevimab-cilgavimab (Evusheld), and the FDA recently warned of its lack of efficacy in this context. The combination is reserved for people with impaired immune systems or severe adverse reactions to vaccination.

Antivirals maintained efficacy over time

BQ.1.1 and XBB were similarly susceptible to the antivirals remdesivir, molnupiravir, and nirmatrelvir as the wild-type virus. The 50% inhibitory concentration (IC50), in this case the level of antiviral needed to neutralize a subvariant, was lower by a factor of 0.6 with remdesivir and higher by factors of 1.1 and 1.2 with molnupiravir and nirmatrelvir, respectively.

For XBB, the IC50 was lower by a factor of 0.8 with remdesivir and by 0.5 with molnupiravir and higher by a factor of 1.3 with nirmatrelvir, suggesting that they are efficacious against both BQ.1.1 and XBB in vitro.

The researchers noted that, compared with older Omicron subvariants, BQ.1.1 and XBB have more mutations in the spike protein, the main target of COVID-19 vaccines and monoclonal antibodies, and thus are more likely to evade immunity. "The continued evolution of omicron variants reinforces the need for new therapeutic monoclonal antibodies for Covid-19," they wrote.

Study shows prone position limited breathing tubes for COVID-19 patients

News brief

Patients admitted to hospital with severe breathing difficulties due to COVID-19 are less likely to need a breathing tube (endotracheal intubation) if they lie face down in a prone position, but the position's effect on mortality or other outcomes is inconclusive, suggests an in-depth analysis of the latest evidence published by The BMJ.

The review included 17 suitable trials involving 2,931 non-intubated COVID patients who were able to breathe without mechanical assistance and who spent an average of 2.8 hours per day lying prone, or on their stomachs.

The authors were particularly interested in gathering evidence from studies that used prone positioning when patients were awake. High-certainty evidence from 14 trials showed that awake prone positioning reduced the risk of endotracheal intubation compared with usual care (24.2% with awake prone positioning v 29.8% with usual care). This translates to 55 fewer intubations per 1,000 patients (95% confidence interval, 19 to 87 fewer intubations), the authors said.

Awake prone positioning was commonly used in the first months of the COVID-19 pandemic.

Thirteen trials examined awake prone positions in the context of mortality outcomes, and they did not show a significant difference in mortality between the two groups (15.6% with awake prone positioning v 17.2% with usual care).

"Awake prone positioning compared with usual care reduces the risk of endotracheal intubation in adults with hypoxemic respiratory failure due to covid-19 but probably has little to no effect on mortality or other outcomes," the authors wrote.

In a related editorial, four medical experts from Toronto write, "Several unanswered questions remain, including the ideal daily duration of treatment, the level of hypoxaemia that should prompt prone positioning, and how best to improve patient comfort and encourage adherence. These questions may never be answered definitively in patients with covid-19 as, fortunately, far fewer are experiencing hypoxaemic respiratory failure or critical illness."

Hospital surveys highlight need for infection prevention and control measures

News brief

Data from five countries show that the hospitals with the highest prevalence of highly resistant microorganisms (HRMOs) implemented the fewest infection prevention and control (IPC) measures, researchers reported this week in Antimicrobial Resistance& Infection Control.

For the study, researchers with the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Nosocomial Infections collected and analyzed survey responses from six hospitals in five countries (Austria, Greece, Italy, Turkey, and the Netherlands) from 2014 to 2017. The surveys asked the participating hospitals to provide prevalence rates for carbapenemase-producing Klebsiella pneumoniae (CPK), carbapenemase-producing Pseudomonas aeruginosa (CPPA), and vancomycin-resistant Enterococcus faecium (VRE), along with detailed information on IPC measures. IPC policies were compared with international IPC guidelines from ESCMID.

The self-reported prevalence of CPK per year was low in the Austrian and Dutch hospitals and high in the Turkish and Greek hospitals. CPPA was highly prevalent in the Turkish hospital only, while the prevalence of VRE in four hospitals—except the Austrian hospitals, which reported lower prevalence numbers—was more evenly distributed. The Dutch hospital reported implementing the most IPC measures (21), and the Turkish and Greek hospitals implemented the fewest (14 and 7, respectively). The hospitals with the lowest HRMO rate also reported a higher adherence to their own IPC policy.

"This study showed that in general, hospitals make different choices in their IPC policy, which could be due to the endemicity of specific HRMO or the lack of logistic or financial resources of a hospital," the study authors wrote. They suggest that investments in higher adherence to IPC policy could help reduce HRMO prevalence.

Measles cases rise in Columbus, Ohio, outbreak

News brief

A measles outbreak in Columbus, Ohio, has grown to 63 cases, up from 50 cases just 3 days ago.

According to an update today from Columbus Public Health, 58 of the 63 confirmed measles cases are in children ages 1 to 5 years, with 43 occurring in children under 2. Sixty of the case-patients are unvaccinated, while 3 have received one dose of the measles, mumps and rubella (MMR) vaccine and are listed as partially vaccinated.

Since the outbreak began in November, 25 children have been hospitalized, with no deaths reported. A department spokesperson told CNN that many of the children have been hospitalized with dehydration.

The list of exposure sites includes a church, department stores in a mall, a grocery store, and a dollar store. Measles symptoms can appear up to 21 days after exposure.

WHO: Malaria cases, deaths remained stable in 2021, despite COVID

News brief

New data from the World Health Organization (WHO) show that malaria cases and deaths remained stable in 2021, easing concerns about the impact of COVID-19–related disruptions to prevention, testing, and treatment services.

According to the latest World Malaria Report, the global number of malaria cases reached 247 million in 2021, compared with 245 million in 2020 and 232 million 2019. There were an estimated 619,000 malaria deaths in 2021, down from 625,000 in 2020 but up from 568,000 in 2019. African nations continued to be hardest hit by malaria, accounting for 95% of cases and 96% of deaths in 2021.

"Following a marked increase in malaria cases and deaths in the first year of the COVID-19 pandemic, malaria-affected countries redoubled their efforts and were able to mitigate the worst impacts of Covid-related disruptions to malaria services," WHO Director-General Tedros Adhanom Ghebreyesus, PhD, said in a press release.

Man hanging mosquito netting
CDC / Gabriel Ponce de León

The report notes that, in 2021, a total of 128 million insecticide-treated nets (ITNs)—the primary vector control tool used in malaria-endemic countries—were distributed, which is comparable to pre-pandemic years. But eight countries distributed less than 60% of their ITNs, and seven countries did not distribute any.

Malaria-endemic countries also distributed 223 million rapid diagnostic tests in 2021, a level similar to what was reported prior to the pandemic, and delivered 242 million artemisinin-based combination therapies (ACTs), up from 239 million in 2019. ACTs are the most effective treatment for malaria caused by the Plasmodium falciparum parasite.

In addition, WHO officials noted that, starting in late 2023, millions of children in the countries hardest hit by malaria will benefit from the world's first malaria vaccine (RTS,S), which has been shown to substantially reduce severe malaria in young children. The WHO has estimated that wide deployment of the vaccine could save the lives of 40,000 to 80,000 African children every year. More than 1 million children in Ghana, Kenya, and Malawi have received the vaccine.

But the agency also cautioned that declining effectiveness of ITNs, parasite mutations that affect the performance of rapid diagnostic tests, and the emergence of artemisinin resistance in Africa could impede further progress against the disease.

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