This week’s digest reprises CDDEP coverage of the big stories of 2016 in antimicrobial resistance and infectious diseases.
: mcr-1, the colistin resistance gene identified in China last November, has been discovered across the globe. Isolates have been identified
in human or animal samples collected in Belgium, Canada, Denmark, France, Germany, Japan, the Netherlands, Thailand, the UK and Vietnam. Many were also resistant to other antibiotic classes, including carbapenems, and many were ESBL producers. An article
(referencing CDDEP’s ResistanceMap
) noted that the prevalence of mcr-1
doesn’t signal the “bacterial apocalypse”—but warns that if current practices continue, it’s not far down the road. [Nature
, National Geographic
Subsequent digest entries covered the discovery of mcr
in the United States (May 27
, June 18
), identification of new variant mcr-1.2
) and discovery of a new colistin-resistance gene, mcr-2
, in Belgium (July 8
: More than 80 pharmaceutical companies, including Merck and GlaxoSmithKline, signed a declaration released at the World Economic Forum in Davos, Switzerland urging governments to invest in development of new antibiotics, vaccines and diagnostics and to develop principles for the conservation of antimicrobials.
CDDEP Director Ramanan Laxminarayan, quoted in a National Geographic article
, commented that the role pharmaceutical companies play in antibiotic conservation—including in the discovery and production of diagnostics and vaccines—is as important as the role companies play in the development of new antibiotics, and greater resources are needed to meet the global threat of resistance. [Bloomberg
, National Geographic
: The World Health Organization has declared the Zika virus epidemic a public health emergency.
Hundreds of thousands of cases are suspected in countries across Central and South America and the Caribbean. The virus has been linked to microcephaly, a serious birth defect, in Brazil, though the country may have fewer microcephaly cases than originally reported
: 1,113 of the 4,783 cases reported since October were re-evaluated, and 709 of the infants did not meet the criteria for microcephaly, while 404 were confirmed. The virus is primarily spread through mosquito bites, though U.S. news organizations reported the first sexually transmitted Zika case in the United States this week. In Brazil, the virus was found in urine and saliva samples
and a blood transfusion-associated case was documented
. The CDC has issued Zika travel notices
for pregnant women to 29 countries and the U.S. territory of Puerto Rico. Pharmaceutical companies Sanofi and NewLink have both announced new efforts to create a Zika vaccine
, though no vaccine could be developed in time for use during the current epidemic. [New York Times
Subsequent digest entries: World Health Organization declares a “strong scientific consensus” that infection with Zika virus causes the birth defect microcephaly and neurological disorder Guillain-Barré syndrome (April 1
); the first US Zika-related death reported in Puerto Rico (April 30
); Zika found to be carried by common Culex mosquitoes (July 23
); US Congress allocates $1.1 billion toward Zika fight (October 2
); WHO declares Zika no longer a public health emergency (November 18
: The world’s first dengue vaccine was administered to schoolchildren in the Philippines starting in April.
The vaccine, Dengvaxia, was created by Sanofi Pasteur
and has been approved for use in Mexico, Brazil and El Salvador in addition to the Philippines. It is approved to prevent all four types of dengue for people aged 9-45 living in endemic areas. In experimental trials, the vaccine reduced the likelihood of contracting dengue by two-thirds. Sanofi Pasteur expects to eventually manufacture 100 million doses of the vaccine per year to meet worldwide demand. [The Wall Street Journal
A subsequent digest entry on this topic covers reports of antibody-dependent enhancement (ADE) from the dengue vaccine, in which a more severe version of the disease can occur after initial infection with one of four strains due to the loss of cross-reactive antibodies to one of the other three strains over time. (August 6
: The antibiotic-free meat industry continues to grow in the United States.
Tyson Foods launched an antibiotic-free line of pork
at the Annual Meat Conference in Nashville. Tyson expects the line to represent less 5 percent of its total pork sales, or up to 1 million antibiotic-free hogs annually. On March 1, restaurant chain giant Subway introduced its first antibiotic-free sub sandwich
, a rotisserie chicken sandwich “made with all white meat, antibiotic-free chicken with no artificial colors or flavor.” Subway plans to have fully antibiotic-free chicken in the United States by the end of 2016 and to eliminate all antibiotics in its meat products by 2025. [Quartz
: The ongoing yellow fever outbreak that began in Angola has spread to the Democratic Republic of the Congo (DRC), where 21 people have died.
In a statement
released this week, the World Health Organization declared that the outbreak “constitutes a potential threat for the entire world.” A global shortage of the yellow fever vaccine, which is produced at only four facilities in the world, has exacerbated the outbreak
. Mass vaccination is the sole strategy for containment, and though a vaccination campaign has reached 6 million out of 7.5 million people living in Luanda, Angola’s capital, travel from the country has spread cases to China, Kenya, the DRC and Mauritania
A subsequent digest entry on this topic covered WHO’s decision not to declare the outbreak a public health emergency (August 20
). As of November 2016, no new cases had been reported in four months. [WHO
May 20: The final report from the UK government-sponsored Review on AMR was released this week,
and includes recommendations for tackling drug-resistant infections worldwide. Lord Jim O’Neill, former chief economist of Goldman Sachs, led the Review
, which offers ten high-level proposals to combat resistance
, combining the goals of limiting inappropriate antimicrobial use, stimulating development of new drugs, and garnering global political will to combat the problem. CDDEP Director Ramanan Laxminarayan commented on the report
for an article in Science News
: “The main reason this may be impactful in ways different from earlier reports is Jim’s background and credibility in financial and government sectors. I hope this report by ‘one of their own’ helps bring attention to the fact that this is not an esoteric medical problem … but rather a global ecological problem that affects us all.” [Review on AMR
, Science News
: CARB-X, a new public-private partnership will stimulate the development of new antibiotics, antimicrobial rapid diagnostics and vaccines
. The partnership, whose full title is Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator, is a $350 million international collaboration between research and development organizations including the Biomedical Advanced Research and Development Authority (BARDA), the National Institute of Allergy and Infectious Diseases, AMR Centre, and the Wellcome Trust. CARB-X Executive Director and Boston University professor Kevin Outterson said, “We’re looking for game-changing products that will make dramatic improvements in human health—not incremental change. We’re going to spend this money on the areas of greatest health need, focusing on things that major pharmaceutical companies have abandoned.” [Boston University
September 9: Sri Lanka has eliminated malaria, against the odds.
Amid more than 20 years of civil conflict, high burdens of the disease, and modest resources, Sri Lanka has managed to eliminate malaria. Sri Lanka is the second country in the WHO Southeast Asia region to reach the malaria-free status, behind Maldives in 2015. Sri Lanka came close to eliminating malaria in 1963, after having 2.8 million cases in 1946, but cases rose in the next four decades, reaching up to a half million cases each year. The country then began an aggressive campaign to treat infected people and fund mosquito control efforts. Dr. Pedro Alonso, Director of the WHO Global Malaria Programme, stated, “It was a hard fight, [but] this is an example to the rest of the world. [Sri Lanka] has sustained this for the last three years in a convincing way.” [Lancet
: World leaders met for the United Nations General Assembly and the UN High-Level Meeting on Antimicrobial Resistance
on September 21, to ratify a political declaration that calls for a global, multisectoral effort to address antimicrobial resistance. Secretary-General Ban Ki-moon called antimicrobial resistance “a fundamental, long-term threat to human health, sustainable food production and development….These trends are undermining hard-won achievements under the Millennium Development Goals
, including against HIV/AIDS, TB, malaria and the survival of mothers and children. If we fail to address this problem quickly and comprehensively, antimicrobial resistance will make providing high quality universal health coverage more difficult, if not impossible.” H.E. Peter Thomson, President of the 71st
session of the UN General Assembly, added, “Member States have today agreed upon a strong political declaration that provides a good basis for the international community to move forward. No one country, sector or organization can address this issue alone.” [WHO
, Political Declaration
: PAHO: Measles has been eliminated in the Americas.
The Pan American Health Organization (PAHO) has declared measles eliminated
in the Region of the Americas, culminating a 22-year effort of mass vaccination against measles, mumps and rubella. Before mass vaccination efforts began in 1980, measles caused nearly 2.6 annual deaths worldwide, with 101,800 deaths attributable to measles between 1971 and 1979 in the Americas. The announcement of its elimination was made by the International Expert Committee for Documenting and Verifying Measles, Rubella and Congenital Rubella Syndrome Elimination in the Americas. [PAHO/WHO
: The malaria death rate in sub-Saharan Africa dropped by 57 percent between 2000 and 2015,
according to an analysis from the Malaria Atlas Project and Global Burden of Disease Study, published in The New England Journal of Medicine.
The analysis used geolocated data for clinical incidence of malaria, coverage of antimalarial drug treatment, case fatality rate, and population distribution according to age. Continent-wide, the malaria mortality rate fell from 12.5 per 10,000 population in 2000 to 5.4 in 2015. Results across countries were mixed, with coverage of insecticide-treated nets and access to treatment less than 50 percent and mortality remaining above 10 per 10,000 in much of Nigeria, Angola, and Cameroon; and in parts of the Central African Republic, Congo, Guinea, and Equatorial Guinea. [New England Journal of Medicine
The tuberculosis burden is much higher than previously estimated.
World Health Organization’s) Global Tuberculosis Report 2016 estimates 10.4 million new TB cases worldwide in 2015. Six countries accounted for 60 percent of the TB burden: India, Indonesia, China, Nigeria, Pakistan, and South Africa, in descending order of case numbers. Through the World Health Assembly and UN General Assembly, governments have agreed on targets to end the TB epidemic, including a 90 percent reduction in TB deaths and 80 percent reduction in cases between 2015 and 2030. According to WHO Director-General Margaret Chan, “We face an uphill battle to reach the global targets for tuberculosis. There must be a massive scale-up of efforts, or countries will continue to run behind in this deadly epidemic and these ambitious goals will be missed.” [WHO release
, Global Tuberculosis Report 2016
: 21st Century Cures Act passed by U.S. Congress.
A massive bipartisan bill passed by the United States Congress includes provisions for improved opioid addiction treatment, additional funding for cancer research and the National Institutes of Health, and a special approval pathway for antibiotics
to treat multidrug resistant (MDR) infections. The bill aims to prevent overprescription of such antibiotics by requiring manufacturers to label them as intended only for a limited population of patients with serious infections and requires manufacturers to submit promotional materials to the Food and Drug Administration (FDA) for approval. The Act also allows for more rapid updating of antimicrobial susceptibility interpretive criteria, “breakpoints,” to help doctors select the most appropriate antibiotic treatment. Although including widely acceptable provisions, the Act has drawn criticism from a number of public health groups and from some legislators, led by Senator Elizabeth Warren, who points to “huge giveaways” to the pharmaceutical industry. She called the additional NIH funding “a mere figleaf,” and possibly not even a real figleaf. [STAT
] [revised 13 December 2016]
NEXT WEEK: A round-up of CDDEP’s biggest stories of 2016, before the digest resumes its usual global scan.