Francesca Tomasi received her B.A. from the University of Chicago and is now a microbiologist.
Hepatitis C (HCV) is a virus that primarily affects the liver. Though it is generally asymptomatic, chronic infection can lead to liver failure, liver cancer, or other life-threatening conditions that typically require a liver transplant. HCV is spread by blood to blood contact, which occurs most frequently through intravenous drug use, poorly sterilized medical equipment, and blood transfusions. Since its emergence, the virus spread silently and went virtually unnoticed. No one was on the lookout for it because nobody knew it existed. After blood transfusions became regular medical practice, however, doctors eventually noticed a rise in liver disease and set out to find the culprit. HCV was identified in 1989.
The isolation of a virus and identification of its cause prompt public health officials to introduce preventive measures. When HCV appeared on the public health radar, clinics began screening blood collected for transfusions, and hospitals in developed countries made sure to sterilize any re-usable needles. However, transmission of HCV still persists today as a result of sharing needles for intravenous drug use (IVDU), sexual intercourse, and accidental contact with infected blood by health care workers. Because of the associations between drug abuse, poor sanitation, and HCV, the disease carries a stigma with it; and while millions of individuals in the United States alone are infected, most do not know it. Those who are at the highest risk are the least likely to present themselves for screening, and people who unknowingly acquired the infection as children do not learn that they have it until they develop symptoms of liver damage later in life.
For a long time, standard treatment for HCV required 48 weeks of weekly interferon injections coupled with oral antiviral pills. Unsurprisingly from such long-term treatments, side effects were the norm, and many people either stopped or refused treatment to avoid fatigue, depression, irritability, and other debilitating conditions. Everything changed in 2013 – or at least, it should have. Two drugs, sofosbuvir (Sovaldi) and simeprevir (Olysio) were FDA approved to treat 3 different types of HCV. The new treatment regimens produce drastic reduction of viral load in just days and have minimal side effects. Last May, the World Health Organization in fact added 5 new HCV drugs on its list of essential medicines. For the first time since it appeared, Hepatitis C could be successfully treated with little to no malaise. But there was a new side effect: some of the treatments cost over $1,000 per pill. Sovaldi, for instance, costs at least $84,000 per regimen in the United States. In February, Gilead Sciences reported that Sovaldi was one of the best-selling drugs in the world in its first year on the market. To compensate for its cost in lower income countries that would otherwise be unable to afford Sovaldi, Gilead has allowed multiple manufacturers to synthesize their product as a generic drug; in India, for instance, eleven generic drug makers produce the drug and sell it in over 90 developing countries (giving Gilead 7% in royalties). Middle-income countries, however, are feeling the strain where generic manufacturers are not authorized to sell Sovaldi. Last May, activists in Argentina, Brazil, China, Ukraine, and Russia demanded voiding the drug’s patent: as officially-recognized developed nations, they do not qualify for purchase of the generic form of the drug. In those 5 countries alone, it would cost over $200 billion to treat over 40 million people with HCV. Sovaldi is financially out of reach for millions of people.
The virus is also on the rise in the United States and its cure unattainable by many. Last May, for instance, the CDC announced a rise in cases in Appalachia. In Kentucky, hepatitis C rates are 7-fold the national average, and these statistics are based only on confirmed cases of the virus, which the CDC estimates account for about 10% of all cases in the country. And since HCV is afflicting more and more young people in America from IVDU and infections passed on from the baby boomer generation, fewer patients are qualified for treatment for a disease that doesn’t cause symptoms until older age. State Medicaid programs only authorize Sovaldi when HCV has progressed to an advanced stage, despite the Infectious Disease Society of America’s recommendation that all diagnosed individuals be qualified for treatment funding.
Thousands of miles away from the Medicaid debates in the United States, a nation in Africa is suffering the aftermath of a decades-long campaign to eliminate the threat of schistosomiasis, a parasitic illness spread by water snails. The campaign succeeded – the disease became less of a threat to the people of Egypt – but it left the country with a potentially bigger problem: hepatitis C spread like wildfire when nurses did not sterilize the needles they used for schistosomiasis vaccines every time they jabbed someone. It is now estimated that about 10% of Egyptians have HCV, the highest rate of infection in the world. Read the New York Times’ recent piece on the fight against hepatitis C in Egypt here to learn more about how the country is battling the disease and its expensive treatment: http://www.nytimes.com/2015/12/16/health/hepatitis-c-treatment-egypt.html?ref=health.
In a world of increasing life expectancies, diseases that take their toll later in life like hepatitis are increasingly important to treat. As we have seen, a huge medical hurdle was cleared a couple of years ago: HCV is now curable, and treatment no longer requires months of nagging side effects. The current financial hurdle is just the next step in Earth’s war on deadly infectious diseases.
Francesca Tomasi received her B.A. from the University of Chicago and is now a microbiologist.
Three years ago, a 2-year-old having recently returned from a trip to India arrived at the Johns Hopkins Children’s Center with persistent fever and malaise. A slew of tests yielded no conclusive diagnosis, until a chest x-ray showed a lung abnormality. Eventually, she was diagnosed with extensively drug-resistant tuberculosis (XDR-TB). This was going to be a difficult case: only a handful of TB cases in young children appear in medical literature, giving from their lungs like adults can, and sputum samples are the main source for diagnostic testing of tuberculosis. Also, ask your toddler to swallow multiple large pills over several months and see how that goes.
Figuring out the child had XDR-TB took about 12 weeks, and the diagnosis was just the start. The physicians at Johns Hopkins dealt first-hand with the limitations of current diagnostic tools, which are time consuming and lack in sensitivity (that is, there are a lot of false negatives). Tracking drug resistance over the disease’s course was another daunting task, and a lack of truly reliable disease markers made it nearly impossible to monitor the child’s response to drug treatment. Monitoring drug treatment was especially important for this pediatric case, since any antibiotics used had to be altered to the physiological and metabolic needs of a two-year-old. This included mushing up the drugs and strategically placing them in her meals.
Enter Dr. Sanjay Jain, Johns Hopkins Children’s Center pediatrician and tuberculosis expert. His team of researchers has been working on real-time imaging techniques to track tuberculosis in patients, methods including CT imaging and PET scanning to track bacterial behavior. Having successfully imaged tuberculosis in mice, it was time to bring the bench to the bedside. Using a child-friendly modification of CT imaging with minimal radiation, clinicians repeatedly performed CT scans of their patient and tracked the progress of her illness over several weeks. A lack of reliable biomarkers for pediatric tuberculosis, Jain explained, prompted his team to turn to this emerging method of live infection imaging. As CT scans over time revealed lower bacterial counts, the patient showed physiological signs of improvement, showing an elegant – and rare – temporal parallel between diagnostic data and physiological response. Now, three years later, the child’s tuberculosis has cleared and she is being monitored to make sure that her infection does not relapse.
This case and its success provide a precedent to the implications of infectious disease imaging, an emerging field with incredible potential to radically improve treatment of all kinds of infectious diseases. Sanjay Jain’s team is one of the pioneering groups working on imaging of infectious diseases (IOI), and has recently developed a way to detect and monitor infections in real-time caused by Gram-negative bacteria. This class of bacteria is physically and physiologically distinct from the acid-fast group to which M. tuberculosis belongs, and increasingly drug-resistant forms of Gram-negative pathogens are responsible for many serious hospital and community-acquired infections.
Jain’s imaging system identifies the source of an infection and allows for real-time tracking of bacterial proliferation, allowing physicians to quickly judge the efficacy of antibiotic therapies in a patient. Because it uses existing technologies and compounds already known to be safe, translation of this work from animal studies to humans is in the near future. The technique works by exploiting a unique metabolic feature of Gram-negative pathogens: these bacteria, which include E. coli, Salmonella, and Klebsiella species, readily consume sorbitol, a compound often found in artificial sweeteners. On the other hand, other microbes and human cells do not absorb sorbitol. Thus, Jain’s team generated radio-labeled sorbitol and incorporated it into a pre-existing PET imaging tracer, which provides a light tag on specific targets. In this case, the researchers’ hypothesis was that Gram-negative bacteria would take up the modified sorbitol and glow on a PET scanner image. Indeed, when Jain’s research team injected mice with live E. coli on one thigh and dead E. coli in the other, the sorbitol-based radio tracer localized to the thigh with live bacteria, and only one thigh lit up on the PET scan. This procedure is pivotal because it discerns between bacteria-induced inflammation and non-pathogenic inflammation, such as something caused by an immune response to a separate trigger.
Being able to rapidly identify the class of organism responsible for a patient’s infection will lead to more appropriate antibiotic choices, and faster. Being able to pinpoint the epicenter of an infection will allow a physician to directly target the source with a specific drug and avoid using broad-spectrum stepping stones that promote drug resistance by challenging all sorts of bacteria living in a person’s body. Furthermore, tracking the light signal of a PET tracer is a simple way to track the efficacy of a therapy: if a signal weakens over time, the drugs are working. If it strengthens or remains constant, a different course of action is due. Rapid feedback against a dynamic source of illness is key to winning the fight. In the end, the patient gets better, the healthcare system spends less money on unnecessary drug treatment, and the bad bugs lose.
Alessandra Tomasi received her B.A. from Cornell University and is now a first year medical student.
Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) affect 1.1 million and 3.2 million individuals, respectively, in the United States alone. 54% percent of new HCV infections are attributed to injection drug use, and approximately 10% of HIV infections fall under this same exposure category. It follows that co-infection with HIV and HCV is common (between 50%–90%) among HIV-infected IDUs. As a result, each year, thousands of individuals are diagnosed with preventable infectious diseases due to the practice of sharing needles. As injection equipment is communal among groups of users, residual blood remaining in syringes is passed on from each individual to the next. However, spreading of the virus is not restricted solely to those physically sharing the contaminated needle— it extends to their partners and children through sexual and perinatal transmissions as well. The proportion of affected individuals therefore remains extensive.
In an attempt to combat these statistics, needle exchange programs have been implemented in several cities around the United States. However, these local efforts continue to be unendorsed on a federal level as accepted forms of intervention, and the allocation of federal funds to such programs remains prohibited by Congress. As a result, NEPs are limited by local or private resources, and their efficacy remains extremely restricted.
The ban on federal support of NEPs by Congress was enacted in the 1980s, and will remain as such until “the Surgeon General of the United States determines that such programs are effective in preventing the spread of HIV and do not encourage the use of illegal drugs.” Numerous countries, however—among which Canada, France, Great Britain, and Australia— have implemented successful, federally funded NEPs. Furthermore, studies across the United States as well as abroad have continued to support the efficacy of such programs. Nevertheless the ban here remains, as policymakers believe that these studies have actually been inadequate in proving the effectiveness of the programs, and that providing clean injection equipment will ultimately promote an increase in drug use in the American public.
If NEPs were instead to be embraced on a federal level, accessibility to sterile needles and syringes would provide a safe means of limiting HCV and HIV transmission among drug users nationwide. Especially for individuals who are unable or unwilling to quit injection drug habits, this remains an extremely promising approach to lessening the burden of infectious disease. On a societal level, too, many of the financial and medical resources currently being used to treat a large proportion of HCV and HIV patients can be reallocated to other cases. In order to lift the ban on federal support and thus allow NEPs to be unrestricted, adequate studies detailing the efficacy of extant programs need to be conducted and presented to policymakers. Alternatively, the supposed limitations of previous individuals studies should be scrutinized in order to determine whether they necessarily disqualify proper conclusions from being drawn.
All in all, federal support of NEPs would allow communities in which such programs are desired to implement them, without the present limitations of minimal resources and funding. Distributing a small amount of money's worth in needles/syringes to prevent diseases that would otherwise cost hundreds of thousands of dollars over a lifetime to treat appears to be a cost-effective and logical approach to reduce the transmission of HIV and HCV among IDUs. However, with a lack of federal support, current and future programs face limitations not only in financial terms, but also in methods of public outreach.