Breakthroughs Blog: Ebola

Photo: National Institute of Allergy and Infectious Diseases (NIAID) Gavi, the Vaccine Alliance, signed an advanced purchase commitment, pledging to spend US$5 million on an Ebola vaccine currently under development by pharmaceutical company Merck & Co. The vaccine candidate was tested on 4,000 people in Guinea last year, and the results were promising: despite all participants having close contact with at least one Ebola patient, none developed the disease more than ten days after vaccination (several days are required for a vaccine to confer protection). The vaccine candidate—VSV-EBOV—was developed and tested in partnership with the Canadian and US governments, however, without the urgency of an outbreak, public-sector support moving forward is limited. The agreement guarantees that there will be a market for the vaccine, assuring Merck & Co. that they can recover investments in advanced development and manufacturing. This move will also enable Gavi to establish a stockpile of the vaccine so that it can be rapidly deployed in future outbreaks. New research suggests that 2.6 million stillbirths occur each year, 420,000 of which are attributable to malaria or syphilis infections. These results underscore the need for testing and treatment of malaria and syphilis in pregnant women, particularly in endemic regions. Fortunately, there are low-cost interventions that could drastically reduce adverse pregnancy outcomes attributable to malaria and syphilis infections. The malaria parasite is able to reside in the placenta, even when undetectable in the mother’s blood, and thus, preventative treatment for malaria is critical. The antimalarial sulphadoxine-pyrimethamine, which costs a mere $0.20 per patient, is recommended for use in pregnant women in endemic areas. In east and southern Africa, an estimated 5 percent of pregnant women are infected with syphilis and in Tanzania, up to half of stillbirths are caused by syphilis. However, one dose of penicillin can cure both maternal and congenital syphilis and prevent stillbirth—at just $1.40 per person. While malaria- and syphilis-related stillbirths can be prevented with the scale-up of existing medicines, many more could be prevented with interventions that are not appropriate for low-resource settings, which is particularly concerning as 98 percent of stillbirths occur in low- and middle-income countries. Further, the cause of stillbirth is often unknown, according to the Global Alliance to Prevent Prematurity and Stillbirth, and additional research is needed to determine and address these causes. There is little incentive for pharmaceutical companies to invest in antimicrobial research and development (R&D): antibiotics are prescribed for short periods of time and competition among antibiotics keeps prices low. However, with the spread of drug resistance, the “[financial] value assigned to antibiotics and diagnostics often does not reflect the benefits they bring to society,” according to a declaration authored by 80 pharmaceutical and diagnostic companies and released at this year‘s World Economic Forum in Davos, Switzerland. The declaration calls on governments to work with the pharmaceutical industry to spur antimicrobial R&D, identifying innovative financing mechanisms, including prizes (a Market Entry Rewards initiative) and intellectual property–related incentives. In response, the companies pledge to invest in R&D for new antibiotics, as well as improved diagnostics to prevent the unnecessary use of antibiotics (i.e., for viral conditions).

A recent clinical trial found that convalescent plasma therapy, a treatment in which the blood plasma is taken from survivors of a disease and used to treat current patients, did not prove to be effective against Ebola. The blood plasma of survivors includes antibodies against the pathogen, in this case the Ebola virus, which can boost a patient’s immune response. Convalescent plasma therapy has been used for more than 100 years, and was first used against Ebola in 1976. In the trial, plasma therapy was used to treat 84 patients, and an additional 418 patients that had been treated at the same facility served as the control group. The treatment reduced death rates by a mere 2.6 percent, and the result was not statistically significant. However, the trial did demonstrate that the collection and transfusion of blood plasma from survivors to patients was safe and feasible in low-resource settings. During the trial, the therapy did appear to be particularly effective in pregnant women and infants, however, the sample size was too small to confirm. Plasma samples from the trial will now be sent to a facility in France where researchers will assess the concentration of antibodies in the samples to determine if the quantity of antibodies affected survival rates. A recent study suggests that the antimalarial artesunate/amodiaquine (ASAQ) could be more effective against Ebola than artemether/lumefantrine (AL), an antimalarial previously used to treat Ebola, due to the diseases’ overlapping symptoms. During the outbreak, a Médecins Sans Frontières treatment center in Liberia initially used AL to treat patients, however, after running out of AL, they began to use ASAQ. The death rate for patients receiving ASAQ was 50.7 percent, compared to 64.4 percent of patients on AL. While ASAQ appears to be a promising treatment, additional trials are needed to investigate ASAQ’s efficacy in reducing Ebola mortality. Strains of the bacteria responsible for the sexually transmitted infection gonorrhea are becoming increasingly resistant to antibiotics. In the United States, one-third of gonorrhea cases are resistant to at least one antibiotic. Public officials, both in the United States and Britain, are urging doctors to follow prescription recommendations to prevent the spread of drug-resistant strains. In Britain, many doctors continue to prescribe ciprofloxacin, which has not been recommended for gonorrhea in 10 years. In the United States, doctors have historically prescribed ceftriaxone, however, between 2011 and 2013—after new guidelines led doctors to prescribe ceftriaxone in combination with azithromycin—ceftriaxone-resistant strains decreased by two-thirds from 1.4 percent to .4 percent of cases. Cow standing in a grassy field. (Photo: PATH/Eric Becker) The bacteria Mycobacterium bovis, which causes bovine tuberculosis (TB), is a rising cause of human TB, and while it’s responsible for just 1.4 percent of cases globally (and 1.5 percent of cases in America), up to 44 percent of TB-infected Latino Americans have the bovine version. Bovine TB is found in two dozen mammal species and is usually transmitted to humans through unpasteurized dairy products. In Mexico, 40 percent of dairy products are unpasteurized, and consequently the proportion of bovine TB cases among Americans are highest along the US-Mexico border. Two-thirds of bovine cases in the United States are extra-pulmonary—outside of the lungs—and are consequently undetectable by standard diagnostic techniques. The remaining third, confined to the lungs, could presumably be spread between humans through coughing or sneezing.