Stewardship / Resistance Scan for Sep 12, 2017

News brief

BARDA provides $32 million for new C difficile drug candidate

The Biomedical Advanced Research and Development Authority (BARDA) has awarded drug maker Summit Therapeutics $32 million over the next 2 years for development of a new antibiotic for Clostridium difficile infection (CDI).

The money will enable UK-based Summit to conduct phase 3 clinical trials of Ridinilazole, an orally administered small-molecule antibiotic that specifically targets C difficile bacteria while leaving beneficial gut bacteria alone, according to a news release yesterday from the Department of Health and Human Services (HHS), BARDA's parent agency. A phase 2 proof-of-concept clinical trial showed that the drug was highly preserving of the microbiome of patients compared the standard of care, vancomycin, and substantially reduced rates of recurrent C difficile.

CDI occurs in patients as a result of prolonged use of wide-spectrum antibiotics, which kill the body's beneficial gastrointestinal flora and allow C difficile bacteria to flourish. Treatment with wide-spectrum antibiotics further disrupts the gut microbiome, which can lead to recurrence. Recurrent CDI occurs in 20% to 30% of patients, with increasing rates of recurrence with each subsequent episode. The Centers for Disease Control and Prevention estimates that C difficile causes nearly half a million infections and 15,000 deaths each year.

Ridinilazole has received Qualified Infectious Disease Product designation from the Food and Drug Administration (FDA), which puts the drug on a fast track for FDA review.

BARDA, an agency within the HHS Office of the Assistant Secretary for Preparedness and Response, is funding the development of Ridinilazole as part of its efforts to develop drugs that treat biothreats such as anthrax and tularemia. Anthrax and tularemia infections require 60 or more days of antibiotic treatment, which can put patients at risk for CDI.

"To save lives from biothreats, whether it's anthrax or tularemia, doctors must be able to treat not just the biothreat itself but also opportunistic secondary infections that may occur,” BARDA director Rick Bright, PhD, said in the HHS release. "Partnering to develop drugs that treat biothreats as well as common, serious infections has proven to be an innovative, sustainable business model for industry and the federal government."
Sep 11 HHS press release
Sep 11 Summit Therapeutics press release

High levels of antimicrobial resistance, dearth of data found in Africa

A systematic review of studies on antimicrobial resistance (AMR) in Africa has found high levels of resistance to commonly prescribed antibiotics. Of greater concern, however, is a lack of recent AMR data for more than 40% of the continent, a finding that highlights the significant knowledge gaps hindering efforts to fully understand the global magnitude of the problem.

The review, published yesterday in BMC Infectious Diseases, identified 144 studies on AMR prevalence and surveillance in Africa published from 2013 through 2016; the selected studies analyzed samples from a total of 149,733 patients. The highest percentage of studies (40.9%) were from countries in East Africa, and the fewest studies (4.2%) were from countries in the South African region. No studies were identified in 23 of 54 (42.6%) countries.

In the 144 studies analyzed, 13 gram-negative and 5 gram-positive bacteria were tested against 37 different antibiotics. Overall resistance to commonly used drugs like amoxicillin (median resistance [MR], 72.9%) and trimethoprim/sulfamethoxazole (MR, 75%), the first-line drugs for urinary tract infections, was high. MR of Escherichia coli, the most common gram-negative bacterium reported, to amoxicillin and trimethoprim was 88.1% and 80.7%, respectively. Among gram-positive bacteria, penicillin resistance in Streptococcus pneumoniae was reported in 14 of 144 studies, with an MR of 26.7%.

Among other significant findings, ciprofloxacin resistance in Salmonella Typhi was rare, and no documented ceftriaxone resistance was reported in Neisseria gonorrhea. Ampicillin resistance in Haemophilus influenzae was high (MR, 100%). Carbapenem resistance was common in Acinetobacter spp and Pseudomonas aeruginosa but uncommon in Enterobacteriaceae. Vancomycin showed the lowest resistance pattern for all tested gram-positive bacteria.

The authors of the study highlight the overall lack of AMR data and note that the lack of consistency in measurement and reporting of susceptibility data makes it difficult to compare findings among different countries. They suggest that standardizing AMR methods and interpretation guidelines "could allow for better comparability of results and improved resistance tracking."
Sep 11 BMC Infect Dis study

News Scan for Sep 12, 2017

News brief

Former CDC head Frieden launches $225 million public health initiative

Tom Frieden, MD, MPH, who stepped down as the director of the US Centers for Disease Control and Prevention (CDC) at the end of the Obama administration, today announced the launch of a $225 million initiative to combat infectious disease outbreaks and heart disease and stroke throughout the world, according to media reports.

The initiative, called Resolve (or Resolve to Save Lives), will be funded by $225 million in backing from Bloomberg Philanthropies, the Chan Zuckerberg Initiative, and the Bill & Melinda Gates Foundation. It will be housed at New York City–based Vital Strategies.

The initiative allows Frieden to tackle some unfinished infectious disease efforts. As part of Ebola response in 2015, the CDC received $1.2 billion for international efforts to bolster countries' capabilities to identify and fight outbreaks.

"Those dollars will expire within the next year or so," Frieden said in a telephone briefing, according to Reuters.

"The Ebola epidemic revealed how vulnerable we are to threats, and was a stark reminder of the human and economic costs caused by the absence of strong public health systems," he added.

"In the preventing epidemics space, we will focus on the 'core four' of surveillance systems, laboratories, trained epidemiologists, and rapid response teams," he told Stat. "And then we can work strategically to identify the countries or in some large countries parts of countries where rapid progress is possible, and the partners who can accelerate that rapid progress."

Why the marriage of infectious disease and cardiovascular health? "The commonality between them is that they’re both at tipping points," he told Stat. "In the next 5 years, it will become clear whether the world has continued to make slow or no progress in each of these areas."
Sep 12 Vital Strategies press release
Sep 12 Reuters story
Sep 12 Stat story

Study: Zika virus can persist in tears for 30 days after illness onset

Researchers in Singapore found that Zika virus can persist in patients' tears for at least 30 days after illness onset, suggesting a prolonged potential for transmission from ocular discharges, according to an article published yesterday in Scientific Reports.

The authors said transmission of Zika virus through tears is uncommon but was noted as a possibility in a previous case study. They also observed that ocular developmental anomalies have been reported in infants with Zika-related microcephaly in Braziland that two cases of Zika-associated uveitis in adult patients have been reported.

For the study, the researchers collected conjunctival swabs from both eyes of 29 adult patients who had confirmed Zika infections in a Singaporean outbreak in August 2016. The swabs were taken 30 days after the patients' recovery. Eight of the patients had conjunctivitis and 3 reported eye pain, but none reported any vision problems.

Using spiked samples, the team determined that their test (quantitative reverse-transcription polymerase chain reaction) was able to detect the virus at concentrations as low as 0.1 plaque-forming units, or 4.9 viral copies, per swab.

Samples from 3 of the 29 patients were positive, with Zika RNA copy numbers ranging from 5.2 to 9.3. The patients were all women, ages 22, 47, and 52 years, though men outnumbered women (16 to 13) in the overall sample.

Two of the three patients who tested positive had conjunctivitis and one had eye pain at the time of sampling, but the third had no evidence of conjunctival inflammation or pain.

The authors said their findings signal that ocular transmission of Zika virus through contact with ocular discharge may be possible even in the late convalescent phase of infection. "It is important to assure that samples of conjunctivae and tears are tested negative for ZIKAV in patients to ensure no risk of virus spread through casual contact," they conclude.
Sep 11 Sci Rep article

CEPI calls for proposals for rapid vaccine production

The Coalition for Epidemic Preparedness Innovations (CEPI) last week announced support for the development of vaccine platforms that will speed production in hopes of making the world better prepared for the next epidemic.

CEPI, in collaboration with the Bill & Melinda Gates Foundation and the US National Institute of Allergy and Infectious Diseases (NIAID), invited research and development institutions, companies, and foundations to submit proposals for new approaches to vaccine development "to radically reduce the time required for the development of new vaccines," the organization said in a news release.

"CEPI will fund vaccine platform technologies that will enable rapid vaccine development, elicit the rapid onset of immunity, and whose production can be scaled up quickly to respond to outbreaks of new or previously unrecognised infectious diseases," the release said.

New platforms should be able to identify a vaccine virus component and be ready for clinical testing in 16 weeks, have the vaccine show clinical benefit within 6 weeks of its first administration, and be able to release 100,000 vaccine doses 8 weeks after production scale-up.

Richard Hatchett, CEO of CEPI said, "Vaccines can be the insurance policy we need to combat that epidemic when it comes. Today's announcement is a call to develop vaccine platform technologies that can rapidly generate safe and effective vaccines against emerging threats. Having such platforms at the ready will represent a major advance in global health security for the whole world."
Sep 5 CEPI news release

Officials report new chikungunya cases in Americas, Italy, Pakistan, India

Chikungunya totals in the Americas have grown by more than 600 cases, according to the latest update from the Pan American Health Association (PAHO), while Italy reported locally transmitted cases for the first time since 2015, and Pakistan and India noted more infections.

PAHO reported 617 new suspected, confirmed, and imported cases, for a total of 145,168 cases so far in 2017. In the previous update the agency reported a drop of more than 28,000 cases as Brazil adjusted its numbers downward as it ruled out suspected cases. Even so, the country accounts for almost 93% of this year's total.

Panama logged the largest increase in cases, with 431 new infections and 2,020 total. Colombia was next with 61 new cases and 858 for the year. Other nations reporting small increases were Mexico, Costa Rica, El Salvador, Nicaragua, Peru, and Ecuador. Among its 25 new cases, Ecuador reported two fatalities, increasing the number of chikungunya-related deaths this year in the region to 88. All the other deaths were in Brazil.

Since the Americas outbreak began in 2013 on St. Martin, the region has now reported 2,531,879 cases.
Sep 8 PAHO update

In Italy, three people in Anzio district, about 30 miles (50 kilometers) south of Rome, have contracted chikungunya locally, BBC News reported on Sep 8. The country first reported a local case in 2007, and its most recent outbreak was in 2015 in northeastern Italy. The district has halted blood donations.

In South Asia, meanwhile, Pakistani officials report that cases in Tharparker district have now topped 2,500, Pakistan Today reported. In April outbreaks in Balochistan and Karachi numbered 1,962 and 1,419 cases, respectively.

And India now has 432 chikungunya cases, officials reported yesterday, according to The Indian Express. In 2016 the country had 12,221 suspected and 9,749 confirmed cases, the story said.
Sep 8 BBC story
Sep 8 Pakistan Today article
Sep 11 India Express report

Journal examines 15 years of public health emergency preparedness

Declaring that the terrorist attacks of September 2001 "forever altered" the understanding of disaster preparedness in the United States, the American Journal of Public Health has published a special issue focusing on public health emergency preparedness efforts over the past 15 years.

The articles in the September issue "provide detailed accounts of preparedness in action, showcasing competencies in biosurveillance, incident management, community resilience, information management, countermeasures and mitigation, and surge management," the editors say in an introductory piece. "These articles demonstrate how and why public health agencies, health care systems, and communities play a vital role in protecting and securing the nation’s public health."

The issue includes 2 introductory pieces and 18 articles on specific preparedness topics. Examples of topics addressed include progress and gaps in addressing pediatric needs in health emergencies, funding for preparedness, mass vaccination in the workplace, pandemic influenza readiness assessment, and preparedness in primary care.
September 2017 Am J Public Health table of contents