CEPI and FIND partner to identify best Nipah and Lassa virus rapid tests

News brief

The Coalition for Epidemic Preparedness and Innovations (CEPI) today announced that it is funding a 4-year project led by the Foundation for Innovative New Diagnostics (FIND) to identify the most reliable rapid tests for Nipah and Lassa virus infections.

Sue Freeman/iStock
Sue Freeman / iStock

Both diseases are among CEPI's priority pathogens, and the group is already funding work on vaccines for both diseases. For the rapid test project, CEPI is granting up to $14.9 million for the work, which is expected to pave the way for licensing the tests for widespread use.

Cassandra Kelly-Cirino, PhD, vice president of FIND's health programs, said the initiative is the first of its kind under the 100 Days Mission of developing tools against future pandemic threats.

"Lack of testing to identify frequent outbreaks of both Nipah and Lassa puts individuals at risk of these deadly diseases as well as posing a threat to whole populations. Having the tools to spot these outbreaks early is critical so that outbreaks can be contained," she said.

So far, Nipah virus outbreaks have been reported from South and Southeast Asian countries, but the fruit bats that spread the virus are found across a wide geographic region covering 2 billion people. The virus can spread from person to person and has a case-fatality rate as high as 70%.

Lassa virus, spread by rats, causes an acute hemorrhagic disease affecting many countries in West Africa.

Long COVID incidence in US varies by state, highest in West Virginia

News brief

Tired woman on exercise bikeNew state and territory surveillance data on long COVID in the United States shows the prevalence of long COVID exceeded 8.8% in seven states and was highest in West Virginia and lowest in the US Virgin Islands.

The study is published today in Morbidity and Mortality Weekly Report.

Nationally, 6.4% of US adults reported ever having experienced long COVID (95% confidence interval [CI], 6.2% to 6.5%). The study was based on information taken from the 2022 Behavioral Risk Factor Surveillance System (BRFSS), a population-based cross-sectional survey.

Long COVID was defined as new or persistent symptoms lasting 3 or more months after a COVID-19 infection.

In general, prevalences of long COVID was lower in New England and higher in the South and West. Montana, Wyoming, and North Dakota all had prevalence rates ranging from 8.9% to 10.6%, as well. West Virginia had the highest rate at 10.6%.

State-level estimates might also help identify geographic disparities in Long COVID across the United States that could guide interventions to promote health equity.

"State-level estimates might also help identify geographic disparities in Long COVID across the United States that could guide interventions to promote health equity," the authors wrote.

WHO to update guidelines for TB preventive treatment

News brief

The World Health Organization (WHO) this week announced updates to its forthcoming guidelines on tuberculosis preventive treatment (TPT).

In a rapid communication, the WHO said the primary update is a recommendation to use a regimen of 6 months of levofloxacin as TPT for contacts of patients with multidrug- or rifampicin-resistant tuberculosis (MDR/RR-TB), based on the results of two randomized controlled trials in Vietnam and South Africa that supported the use of the regimen in all age-groups.

Other revisions include updated drug dosages for TPT regimens with levofloxacin and rifapentine, integration of recommendations on screening strategies to rule out TB ahead of starting TPT and the use of TB tests, and an update of the algorithm for the management of TPT in contacts.

The updated guidelines will be released later this year.

"This Rapid Communication is being issued to help national TB programmes and other stakeholders prepare for the changes that will be introduced with the update of guidelines on TPT," the WHO said.

Scaling up TPT is considered a critical component of the WHO's End TB Strategy. In September 2023, United Nations (UN) Member States committed to increasing TPT coverage among contacts and people with HIV, with a goal of reaching 45 million people by 2027. 

Antibiotic combination shows superiority to meropenem for complicated urinary tract infections

News brief

An antibiotic combination designed to target difficult-to-treat gram-negative bacteria was superior to meropenem in patients with complicated urinary tract infection (UTI), according to the results of a phase 3 trial published today in the New England Journal of Medicine.

Cefepime-taniborbactam combines a fourth-generation cephalosporin antibiotic with a beta-lactamase inhibitor. Developed by Venatorx Pharmaceuticals of Malvern, Pennsylvania, the combination has shown in vitro and in vivo efficacy against carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa, with an acceptable side-effect profile in healthy volunteers.

Venatorx submitted a New Drug Application to the US Food and Drug Administration in August 2023 based on the results of the trial, which were first announced in November 2022.

In the double-blind trial, adults with complicated UTIs, including acute pyelonephritis, in 15 countries were randomized 2:1 to receive intravenous cefepime-taniborbactam or meropenem every 8 hours for 7 days. The primary outcome was both microbiologic and clinical success (composite success) on trial days 19 and 23 in the microbiologic intention-to-treat (microITT) population.

Composite success against carbapenem-resistant isolates

Of the 661 patients who underwent randomization, 436 (mean age, 56.2 years) were included in the microITT population. Of those patients, 57.8% had complicated UTI, 42.2% had acute pyelonephritis, and 13.1% had bacteremia. Enterobacterales accounted for 95.9% of baseline pathogens, and P aeruginosa 4.1%.

Composite success occurred in 207 (70.8%) of 293 patients in the cefepime-taniborbactam group and 83 (58.0%) of 143 patients in the meropenem group. The treatment difference (12.6 percentage points; 95% confidence interval, 3.1 to 22.2) met the superiority criteria for the primary outcome. The difference in treatment response was sustained at late follow-up (trial days 28 and 35), with cefepime-taniborbactam showing higher composite success and clinical success. The combination also had composite success in 8 of 10 patients with meropenem-resistant isolates.

Adverse events occurred in the 35.5% of patients in the cefepime-taniborbactam group and 29.0% in the meropenem group. The frequency of severe adverse events was similar in both groups.

"Thus, cefepime–taniborbactam was shown to be a potential treatment option for patients with complicated UTI and acute pyelonephritis caused by Enterobacterales species and P. aeruginosa, including antimicrobial-resistant strains," the investigators concluded.

Researchers identify episodic MERS cases in Kenyan camels, evidence of infection in people

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Year-long sampling of dromedary camels in northern Kenya reveals biphasic (two-phase) peaks of Middle East respiratory syndrome coronavirus (MERS-CoV) and identifies more than three case clusters over 3 weeks in camels from different areas, as well as a 15% infection rate in slaughterhouse workers.

For the study, published yesterday in Emerging Infectious Diseases, a University of Nairobi–led research team sampled 10 to 15 camels from 12 different regions 4 or 5 days a week from September 2022 to September 2023.

MERS is a respiratory disease caused by a relative of SARS-CoV-2, the coronavirus that causes COVID-19. MERS can cause severe lung infection, fever, cough, shortness of breath, and death. It was first discovered in humans in Saudi Arabia in 2012 and has since spread to many other countries. There is no vaccine against MERS, and treatment consists of supportive care.

MERS-CoV RNA found in 1.3% of camels

Reverse transcription-polymerase chain reaction (RT-PCR) detected MERS-CoV RNA in 1.3% of camels. The incidence peaked in early October 2022, at 11.7%, and February 2023 (12.1%), corresponding to Kenya's dry seasons, when camel calves lose their maternal antibodies.

On enzyme-linked immunosorbent assay (ELISA), MERS-CoV IgG levels in 369 random samples showed an 80.8% seroprevalence of immunoglobulin G (IgG) antibodies. IgG levels were lowest in June and highest in March. IgG levels were negatively associated with RNA positivity.

Identifying defined factors that drive MERS-CoV outbreaks will assist in predictive epidemiology, risk assessment, and timely precautionary interventions for public and occupational health.

IgG reactivity was identified in 7 of the 48 slaughterhouse workers (14.6%), with 1 of them showing evidence of MERS-CoV neutralizing antibodies. None were severely ill.

"Our sustained sampling of dromedary camels showed a biphasic MERS-CoV incidence in northern Kenya not observed in previous studies," the researchers said. "One explanation might be the short time of virus excretion in MERS-CoV–infected dromedaries, making viral RNA detection difficult without daily surveillance."

Increased camel-to-camel interactions between unexposed and infected animals from different herds in slaughterhouses could have influenced the outbreaks, the authors said.

"Rapid point-of-care tests might help trace infections even in resource-limited conditions," they wrote. "Identifying defined factors that drive MERS-CoV outbreaks will assist in predictive epidemiology, risk assessment, and timely precautionary interventions for public and occupational health."

New COVID antiviral candidate linked to shorter symptoms

News brief

Treatment with ensitrelvir, an oral SARS-CoV-2 3C-like protease inhibitor developed in Japan, shortened COVID-19 symptoms in people who received the medication within 3 days of symptom onset, researchers reported recently in JAMA Network Open.

woman taking pills
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In 2023, the drug—made by Shionogi—was authorized for emergency use in Japan and received a fast-track review designation from the US Food and Drug Administration.

The randomized clinical trial took place between February 2022 and July 2022 when the Omicron BA.2 variant was circulating at clinical sites in Japan, Vietnam, and South Korea. The study population included mostly healthy people ages 12 to 69 years old who had mild to moderate COVID symptoms and a positive test for the virus. About 91% had previously received two doses of COVID vaccine.

Researchers evaluated two different ensitrelvir doses given for 5 days against placebo. One dose was 125 mg given once a day (375 mg on the first day), and the other was 250 mg once daily (750 mg on the first day). Researchers followed the groups for 28 days, monitoring symptoms including runny nose, sore throat, shortness of breath, and cough, as well as any side effects.

Symptoms shortened from 5 days to 4 days

They saw a significant difference between the 125-mg dose and placebo, with treatment shortening symptoms by 1 day, from 5 days to 4 days. There were no serious adverse events, but people who took ensitrelvir had temporary reductions in their high-density lipoprotein levels. In the secondary analysis, treatment also reduced viral loads when compared to placebo.

The team said more studies need to be done to assess efficacy in populations outside of Asia and in people who have a range of different risk factors.

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