Sanofi updates information on dengue vaccine 29 November 2017 (Sanofi Press Release) Based on up to six years of clinical data, a new analysis evaluated long-term safety and efficacy of Dengvaxia in people who had been infected with dengue prior to vaccination and those who had not. The analysis confirmed that Dengvaxia provides persistent protective benefit against dengue fever in those who had prior infection. For those not previously infected by dengue virus, however, the analysis found that in the longer term, more cases of severe disease could occur following vaccination upon a subsequent dengue infection. About half of the world s population lives in countries where four serotypes of dengue virus are in circulation. People can be infected with dengue up to four times in their lifetime and they can get severely ill after any of these infections. Surveillance data from some endemic countries indicate that between 70 and 90 percent of people will have been exposed to dengue at least once by the time they reach adolescence. There are many factors that can lead to severe dengue infection. However, the highest risk of getting more severe disease has been observed in people infected for the second time by a different dengue virus. Dengvaxia is currently indicated in most of the countries for individuals 9 years of age and older living in a dengue-endemic area. In this indicated population, Dengvaxia has been shown to prevent 93 percent of severe disease and 80 percent of hospitalizations due to dengue over the 25 month phase of the large-scale clinical studies conducted in 10 countries in Latin America and Asia where dengue is widespread. Based on the new analysis, Sanofi will propose that healthcare professionals assess the likelihood of prior dengue infection in an individual before vaccinating. Vaccination should only be recommended when the potential benefits outweigh the potential risks (in countries with high burden of dengue disease). For individuals who have not been previously infected by dengue virus, vaccination should not be recommended. Editorial comment: As a result of this information, the immunization program with Dengvaxia in the Phillipines was halted after the immunization of about 830,000 children ages 9 and above. The concern is over anti-dependent enhancement (ADE) with a more severe course. ADE is classically seen when an individual has dengue fever which elicits protective antibody against that serotype and cross elicits non-protective antibody against the other 3 serotypes. If infection occurs with a different serotype of dengue, antibody-dependent enhancement (ADE) may result with a severe course (e.g. dengue hemorrhagic fever). Dengvaxia was meant to provide protection against dengue to those vaccinated, including those who did not have any prior dengue infection. However, in those not previously exposed, it apparently may predispose some to ADE. According to Thomas Yuill a ProMED-mail virus moderator, The concern about more severe dengue infections in vaccinated children who experience their first natural infection is due to ADE of that infection. ADE can occur in individuals who have antibodies that are not neutralizing but are able to attach to the virus and bind them to cells that are susceptible to Published by Oxford University Press for the Infectious Diseases Society of America 2018.
infection, enhancing that infection. Since Dengvaxia vaccinations are not 100 percent effective in preventing dengue virus infection in nature and yet induce antibodies to dengue virus, there may be a small proportion of vaccinated children in whom ADE and more severe natural infections may occur. If the child has already had one or more wild-type DENV infections, the immune system is already primed and the tetravalent vaccine provides a boost that helps to provide more solid immunity against a different wild-type DENV that the child may be exposed to. The practical challenge in restricting vaccination to children who have already had one or more dengue virus infections is determining who has had those previous infections and who has not. There is no quick, cheap and reliable test available that can be administered in vaccination clinics filled with children awaiting their shots. See (http://science.sciencemag.org/content/early/2017/11/01/science.aan6836). The question is whether to throw out the baby with the bath water. Can systems be developed to do on site measurement of antibody before immunization? Is prevention of dengue fever with an imperfect vaccine worth an occasional case of ADE? There is also concern that Dengvaxia could produce ADE in Zika infection as anti-dengue antibodies cross react with Zika virus. The World Health Organization has advised that pending review, Dengvaxia only be given to people known to have been infected with dengue prior to vaccination.
Diphtheria update (Prepared by the section editor) Diphtheria, a vaccine preventable disease, is currently wreaking havoc in a number of countries. Yearly counts for 2017 are given for the following countries: as of 4 December, Yemen has reported 318 suspected cases with 28 deaths; as of 7 December, Indonesia has reported 591 cases with 32 deaths; and as of 16 December, Venezuela, which once had an outstanding medical care system, has reported 609 probable cases of diphtheria, with over a 20% mortality rate. In Haiti, the outbreak, which began at the end of 2014, has continued with now a total of 348 probable diphtheria cases that include 46 deaths. As of December 2017, there have been 2373 cases, including 21 deaths, reported among the displaced Rohingya population in Bangladesh. Children are at highest risk, but adults are not spared. In all of these countries, there has been a failure of immunization programs either due to war, poverty displacement of populations or mismanagement by the government or a combination of these. Although diphtheria is new for Venezuela, Indonesia, along with India and Madagascar, has had the world s highest case counts of diphtheria. For example, both India and Madagascar had about 3000 cases in 2016.
Progress Toward Global Eradication of Dracunculiasis, January 2016 June 2017 (MMWR 66:1327, 2017) Dracunculiasis (Guinea worm disease) is caused by Dracunculus medinensis. Approximately 1 year after a person acquires infection from contaminated drinking water, the worm emerges through the skin, usually on a lower limb. In 1986, the World Health Assembly called for dracunculiasis elimination. In 1986, an estimated 3.5 million cases occurred each year in 20 countries in Africa and Asia. Since then, considerable progress has been made. Compared with the 1986 estimate, the annual number of reported cases in 2016 has declined by >99%, and cases are confined to three countries with endemic disease. In 2016, a total of 25 cases were reported from three countries (Chad [16], South Sudan [six], Ethiopia [three]). During the first 6 months of 2017, the overall number of cases declined to eight, all in Chad. Because the life cycle of D. medinensis is complex, its transmission can be interrupted using multiple strategies. Dracunculiasis can be prevented by the following four main interventions: 1) educating residents in communities where the disease is endemic, particularly persons from whom worms are emerging, to avoid immersing affected body parts in sources of drinking water; 2) filtering potentially contaminated drinking water through a cloth filter or pipe filters to remove copepods (small crustaceans that host D. medinensis larvae); 3) treating potentially contaminated surface water with the organophosphate insecticide temephos (Abate) to kill the copepods; and 4) providing safe drinking water from bore-hole or protected hand-dug wells. Containment of transmission is achieved through four complementary measures: 1) voluntary isolation and education of each patient to prevent contamination of drinking water sources, 2) provision of first aid to prevent secondary infections, 3) manual extraction of the worm, and 4) application of occlusive bandages. No vaccine or medicine to prevent or treat Guinea worm disease currently exists. Editorial comment: Two diseases have been totally eradicated, smallpox and rinderpest, a disease of ruminants. Dracunculiasis will probably be the third. However, the reservoir in dogs poses a problem. Availability of safe drinking water is the way to guarantee eradication.
Antibiotics sales for use in U.S. farm animals dropped in 2016: FDA 8 December 2017 (Reuters [Theopolis Waters]) The sale and distribution of antibiotics approved for use in food-producing animals in the United States decreased by 10% from 2015 to 2016, a U.S. Food and Drug Administration (FDA) report said. It was the first decline in year-to-year sales since the FDA began collecting the data in 2009, according to food and consumer health groups. Major U.S. food companies including McDonald s and Tyson Foods have stepped up efforts to curtail, and in some cases eliminate, antibiotics in their products. An estimated 70% of the kinds of antibiotics that are also used to fight human infections and in surgery are sold in the United States for use in meat production. In 2016, sales and distribution of those medically important antibiotics for food production fell 14%, the FDA said. Medically important antimicrobials accounted for 60% of the domestic sales of all antimicrobials approved for use in farm animals in 2016, the agency said. The FDA s data show chicken accounting for 6% of medically important antibiotic sales, with swine at 37% and cattle at 43%. Avinash Kar, senior attorney at environmental activist group the Natural Resources Defense Council, attributed the progress to significant changes undertaken by the chicken industry. He said the pork and beef sectors lag behind. Tyson Foods, the nation s leading meat producer, this year became the world s largest producer of no-antibiotic-ever chicken. Copyright 2017 Reuters Limited. All rights reserved.