Breakthroughs Blog: Research Roundup

Last week, an oral cholera vaccine receivedWorld Health Organization (WHO) prequalification, a process of regulatory review which paves the way for procurement by United Nations agencies and international organizations. Up to 4.3 million cases and 142,000 deaths from cholera are reported annually, primarily in low- and middle-income countries, and the vaccine—Euvichol®—is 65 percent effective against the bacteria. Euvichol® was developed by GHTC member the International Vaccine Institute (IVI), and has been licensed to the Korean company Eubiologics, which plans to produce 6 million doses in 2016. The vaccine is a reformulated version of Shanchol™, which is licensed to Shantha Biotechnics in India, and was prequalified in 2011. According to the WHO, prequalification of Euvichol® could double the global supply of cholera vaccines. Euvichol® produced by EuBiologics. Photo: IVI Scientists have identified three compounds that could serve as the basis for a vaccine against onchocerciasis (river blindness). More than 17 million people globally are affected by river blindness, 70 percent of whom experience skin conditions, including itching and lesions, and 10 percent of whom develop eye conditions, leading to visual impairment. Without a vaccine, river blindness control programs use the antiparasitic drug ivermectin to treat the disease, however, ivermectin is not recommended for use in children under five. Additionally, in Central and Western Africa, where coinfection with Loa loa worms is common, use of ivermectin can lead to fatal brain inflammation. The team hopes to initiate safety and efficacy trials for a potential vaccine candidate by 2020 and 2025, respectively. The Global Fund to Fight AIDS, Tuberculosis and Malaria is launching an “e-marketplace” through which global health product procurers (i.e., governments and nongovernmental organizations) can purchase everything from drugs and diagnostics to condoms and cars. The e-marketplace will be an online platform utilizing the Global Fund’s pooled procurement mechanisms. Through this mechanism, the Global Fund negotiates with manufacturers and purchases large quantities of global health commodities; governments and other organizations are then able to purchase products directly from the Global Fund, reducing product and transaction costs. This approach also improves demand forecasting and ensures a sustainable supply of products. The launch of the e-marketplace will be phased: while in the first quarter of 2016, only bednets will be available, artemisinin combination malaria medicines, malaria and HIV and AIDS diagnostics, and antiretrovirals will be available by the end of the year. The e-marketplace will initially be limited to Global Fund grant recipients, and 10 to 20 countries are expected to utilize the platform in 2016. The Global Fund hopes to open the e-marketplace to more buyers in the future and eventually offer products that are not part of Global Fund agreements, enabling procurers to independently compare quotes from different manufacturers.

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.

Photo: Neil Brandvold/DNDi Global Health Now took an in-depth look at the flesh-eating fungus mycetoma—which enters the body through cuts, and can result in swollen, deformed limbs—in a three-part series on this Untold Global Health Story of 2015. The final installation focuses on GHTC member Drugs for Neglected Diseases initiative (DNDi), a product development partnership that will be initiating a clinical trial in mid-2016 to assess the safety and efficacy of the antifungal Fosravuconazole against mycetoma. Fosravuconazole is currently under development by Japanese pharmaceutical company Eisai, where it has proven more successful at combatting mycetoma in petri dishes than currently used medicines. The leading treatment, itraconazole, is only curative for one in thirteen patients after a year of use. The article notes that DNDi’s entire budget for the study is under US$2 million, compared with the average $1 billion spent by pharmaceutical companies. Eisai has agreed to donate Fosravuconazole pills for the trial which will compare Fosravuconazole, itraconazole, and a placebo. Pharmaceutical company Gilead Sciences has been heavily criticized for “price gouging,” charging Americans $1,000 per pill for their drug sofosbuvir, which, for most patients, cures Hepatitis C in twelve weeks. However, in Egypt, where 10 percent of the population has chronic Hepatitis C—the highest rate worldwide—Gilead is selling them to the government for $10 per pill. The reduced price comes at a cost: to prevent the drugs from entering the black market and undermining Gilead’s sales, the Egyptian government has agreed to several restrictions that some advocates consider humiliating for patients and/or unethical. Not only are the drugs only sold at official government pharmacies, but patients must break the seal and take the first pill on-site to receive their first bottle and must return the original bottle to receive refills. The program has generated interest from other pharmaceutical companies, and the government has entered into similar deals with Bristol-Meyers Squibb and AbbVie, importing their medicines Viekira and Daklinza, respectively. Over the past year, more than 125,000 Egyptians have been treated, and the government hopes to treat another 300,000 each year starting in 2016, with the ultimate goal of reducing prevalence to 2 percent by 2025. Figure 1: Compounds included in the Pathogen Box, by disease (Photo: MMV) GHTC member Medicines for Malaria Venture (MMV) launched the Pathogen Box, a set of 400 compounds, each with proven activity (i.e., in test tubes) against neglected diseases, free for researchers and laboratories around the world. To create the Pathogen Box, MMV's team of chemists, as well as partners with expertise across neglected diseases, evaluated compounds in the European Bioinformatics Institute’s open access database, to determine those with the most potential. The team then acquired fresh samples of each compound to include in the boxes themselves. By expanding access to these samples, the Pathogen Box eliminates a major barrier to drug discovery for malaria, tuberculosis, schistosomiasis, Chagas, and other neglected diseases (See Figure 1).

Virginia Commonwealth University (VCU) received a grant from the Global Alliance to Prevent Prematurity and Stillbirth, a member of the GHTC, to study the human microbiome in search of biomarkers to predict preterm birth. The human microbiome is comprised of all the microorganisms (i.e., bacteria) normally found in the human body and the genetic material of those microorganisms. The team at VCU will study the microbiome of women throughout pregnancy, assessing the impact of changes in the microbiome on pregnancy outcomes. Existing research has demonstrated a correlation between an imbalance in the vaginal microbiome of pregnant women and preterm birth, specifically for African Americans. A recent study out of The Rockefeller University in New York could pave the way for a new treatment against human African trypanosomiasis (sleeping sickness), a disease caused by the Trypanosoma brucei parasite and transmitted by the tsetse fly. Once in the human bloodstream, the parasite evolves, and constantly changes the proteins on its surface so that the immune system can’t recognize it. The team at The Rockefeller University determined that by blocking bromodomains—a particular type of protein—through either genetic modification of the parasite or the use of a molecule known as I-BET151, they could trick the parasite into thinking it was still in the tsetse fly. Thus, the parasite would revert to the form it takes within the fly, making it much easier for the immune system to detect and attack it. The method was tested in sleeping sickness–infected mice, and those treated with I-BET151 survived much longer than their counterparts. Child receiving a vaccine. Photo: PATH/Robin Biellik The world’s first vaccine against dengue fever—a mosquito-borne disease that causes fever, headache, and, muscle and joint pain—has been approved for use in people aged 9 to 45 by the national regulatory authority of Mexico. Nearly half the world’s population lives in dengue-endemic countries, and an estimated 390 million infections occur each year. The vaccine, which cost US$1.65 billion to develop over 20 years, is projected to generate $1.4 billion in sales by 2020. Sanofi, the pharmaceutical company that developed “Dengvaxia,” is currently pursuing regulatory approval in 19 other countries and has stated that the vaccine will be sold at a “fair, affordable, equitable, and sustainable price.”