C difficile vaccine candidate fails to meet primary end point in phase 3 trial

News brief
Clostridioides difficile
Jennifer Oosthuizen / CDC

A Clostridioides difficile vaccine candidate was safe, well tolerated, and reduced C difficile infection (CDI) severity but did not reduce incidence of CDI in at-risk adults, according to the results of a phase 3 randomized clinical trial published late last week in Clinical Infectious Diseases.

The global, phase 3 CLOVER trial, conducted in 23 countries from March 2017 through December 2021, assessed the efficacy of PF-06425090, a genetically detoxified toxin C difficile vaccine candidate from Pfizer, in adults 50 and older who were considered at increased CDI risk. Overall, 17,535 participants (mean age, 68; 51.5% female; 79.2% White) were randomized to receive three doses of PF-06425090 or placebo. The primary end points were the first CDI episode 14 or more days post–dose three (PD3) and post–dose two (PD2). CDI duration, need for CDI-related medical attention, and antibiotic use PD3 were also evaluated.

Among the participants who received all three doses, 17 PF-06425090 and 25 placebo recipients had a primary CDI episode 14 or more days PD3, resulting in vaccine efficacy (VE) of 31%, but the 96.4% confidence interval ranged well below 0. Among those who received two doses, 24 PF-06425090 and 34 placebo recipients had a first CDI episode 14 or more days PD2, for a VE of 28.6%, with a similarly wide confidence interval. Median CDI duration was lower with PF-06425090 (1 day) versus placebo (4 days). Of participants with a first CDI episode, 0 PF-06425090 and 11 placebo recipients sought CDI-related medical attention (post-hoc analysis estimated VE, 100%) and 0 PF-06425090 and 10 placebo recipients required antibiotic treatment (VE, 100%). 

Local reactions were more frequent in PF-06425090 recipients, while systemic events, most of which were mild-to-moderate, were generally similar between groups. Adverse event rates were similar between groups.

Potential public health benefit

The trial investigators say that while the primary end point wasn't met, the results suggest PF-06425090 could provide a public health benefit.

"Together, these findings suggest PF-06425090 may reduce overall disease burden by potentially reducing CDI severity in vaccine recipients and consequent need for medical interventions," trial investigators wrote. "Limiting need for medical attention not only alleviates healthcare resource strains but reduces potential for antibiotic exposure, which may help mitigate increasing global threats of antimicrobial resistance."

Avian flu virus confirmed in Michigan dairy herd

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dairy cows
Sabrina Gordon/iStock

Highly pathogenic avian influenza (HPAI) virus has been confirmed in a dairy herd in Van Buren County, Michigan—the nation's first detection for almost 2 weeks. The last detection in Michigan was on July 26, also in Van Buren County. 

The detection brings the number of affected dairy herds in Michigan to 28, and samples have been sent to the US Department of Agriculture's (USDA) National Veterinary Services Laboratories for additional confirmatory testing, according to the Michigan Department of Agriculture & Rural Development.

According to state rules, the detection will now prohibit the exhibition of all lactating dairy cattle, and those in the last 2 months of pregnancy, until there are no new cases of HPAI in Michigan dairy cattle for at least 60 consecutive days.

In the past 30 days, 5 states have reported 20 cases of HPAI in dairy cattle, according to the USDA. The most recent previous detections were in Colorado and Idaho. 

Study suggests antibodies to flu common in raptors 

In other avian flu news, a preprint study of raptors from the University of Minnesota's Raptor Center and the Hawk Ridge Bird Observatory in Duluth during the 2022-23 H5N1 avian flu outbreak finds that 69.1% of bald eagles were seropositive for influenza virus, and 52 of 67 (77.6%) of them tested positive for antibodies to both H5 and N1.

The study, which has not yet been peer-reviewed, offers new insight on the seroprevalence of influenza viruses in wild birds. According to the authors, the prevalence of influenza antibodies observed in this study was higher than reported from raptors sampled in this same region in 2012

Massachusetts to start spraying for Eastern equine encephalitis

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Mosquito
D Sikes / Flickr cc

Massachusetts officials over the weekend announced plans to start spraying for mosquitoes in two counties to reduce the risk from eastern equine encephalitis (EEE). 

Officials from the Massachusetts Department of Health (DPH) and the Massachusetts Department of Agricultural Resources said they will conduct aerial spraying in parts of Plymouth County and truck-mounted spraying in parts of Worcester County to target mosquitoes carrying the virus. On August 16, the DPH reported the state's first EEE case since 2020, in a man in his 80s who was exposed in Worcester County.

EEE is a rare but serious mosquito-borne illness that can lead to severe neurologic complications and potentially be fatal. In the 2019-20 EEE outbreak in Massachusetts, 17 cases and 7 deaths were reported.

"We have not seen an outbreak of EEE for four years in Massachusetts," DPH Commissioner Robbie Goldstein, MD, PhD, said in a DPH press release. "This year's outbreak and activity raise the risk for communities in parts of the state. We need to use all our available tools to reduce risk and protect our communities."

DPH officials are also advising residents of high-risk areas to schedule outdoor activities to avoid dusk-to-dawn hours to minimize exposure to the mosquitoes most likely to carry EEE.

West Nile virus also a concern

In a separate press release, the DPH said eight municipalities are now to be considered at high risk from another mosquito-borne illness—West Nile virus (WNV). The first WNV-positive mosquitoes in Massachusetts were announced on July 2. 

"We are finding evidence of West Nile virus in mosquitoes in multiple parts of the Commonwealth," Goldstein said. "While most people do not get severely ill from WNV, it is still important to take it seriously."

The elevated risk level applies to Boston in Suffolk County and Abington, Brockton, East Bridgewater, Marion, Mattapoisett, Rochester, and Whitman in Plymouth County.

Efforts to reduce antimicrobial resistance in low-resource nations are lagging, survey suggests

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A survey of public health experts from low- and middle-income countries (LMICs) highlights significant gaps in implementation and enforcement of policies aimed at mitigating antimicrobial resistance (AMR), researchers reported late last week in BMC Public Health.

The Global Survey of Experts on Antimicrobial Resistance (GSEAR), developed by researchers with the Swiss Tropical and Public Health Institute and University of Basel, was sent to public health experts in 138 LMICs to assess their countries' efforts to address AMR. The main areas covered by the survey were existence of AMR national action plans (NAPs), policies and interventions to restrict the sale and consumption of antibiotics, current antibiotic use, antibiotic prescribing practices, collection and reporting of surveillance data, and AMR awareness.

A total of 352 surveys from 118 LMICs were analyzed. Experts in 67% of the surveyed countries reported a NAP on AMR, 64% reported legislative policies on antimicrobial use, 58% reported national training programs for health professionals, and 10% reported national monitoring systems for antimicrobials. Fifty-one percent of LMICs had specific targeted policies to limit the sale and use of protected or reserve antibiotics. While 72% of LMICs had prescription requirements for accessing antibiotics, getting antibiotics without a prescription was reported to be possible in 74% of LMICs. 

Government officials may overestimate policy coverage

When the researchers compared the GSEAR results to the 2020-21 World Health Organization–organized Tripartite AMR Country Self-Assessment Survey (TrACSS), which was completed by government officials in 113 LMICs, they found substantial disagreement. For example, TrACCS results indicated 86% had NAPs and 86% had legislative policies on antimicrobial use. 

Based on expert perspectives, there are significant gaps in current policy and implementation efforts to address AMR in LMICs, with a large number of countries falling short of target achievements.

The authors say that while the experts consulted in the GSEAR survey may not always be aware of NAPs and specific policies and programs in their respective countries, the gaps between the GSEAR at TrACSS responses suggests countries may be overestimating their efforts.

"Based on expert perspectives, there are significant gaps in current policy and implementation efforts to address AMR in LMICs, with a large number of countries falling short of target achievements; current policy coverage may be substantially lower than what the TrACSS survey suggests," the authors wrote.

India reports largest Chandipura virus outbreak in 2 decades

News brief

India has reported a surge in Chandipura virus infections this summer, with 245 acute encephalitis syndrome (AES) cases reported since July, with 82 of them fatal. So far, polymerase chain reaction testing has confirmed the virus in 64 cases, the World Health Organization (WHO) said in an August 23 outbreak announcement.

sandfly
Insect vectors include sandflies. USDA/Stephen Ausmus/Flickr cc

Chandipura virus is endemic in India, and it is known to trigger sporadic cases and outbreaks of AES in western, southern, and central part of the country, especially during monsoon season. Outbreaks typically occur every 4 to 5 years in Gujarat state. The virus—a member of the Rhabdoviridae family—is transmitted by vectors that include sandflies, mosquitoes, and ticks.

Children most affected; fast onset of severe symptoms

The disease mainly affects children ages 15 and younger. The main symptoms are fever, with coma and convulsions that can occur within 48 to 72 hours of symptoms onset.

Cases began rising in early June, and 43 of 806 districts in India have reported AES cases. Of the 64 confirmed cases, 61 were in Gujarat state and 3 in Rajasthan state. 

The WHO said cases have been declining since the middle of July. Though authorities have deployed control strategies, further transmission is possible in the coming weeks, given favorable conditions from the monsoon season in affected areas.

India's last large Chandipura virus occurred in 2003, when 329 suspected cases, 183 of them fatal, were reported in Andhra Pradesh state. The virus has been detected only in India, but the WHO said it may be present in other countries in Asia and Africa. The sandfly vector is present in Southeast Asia.

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