Research Roundup: Malaria and bone density, a fatal vaccine error, and a sponsored Chikungunya trial

Typhoid may seem like a distant memory in industrialized countries, but for many low- and middle-income countries (LMICs) it continues to cause millions of illnesses and about 150,000 deaths per year in endemic areas and during outbreaks. Spread through contaminated food and water, typhoid typically burdens young children and adolescents under the age of 15. Recently, we have witnessed several outbreaks, including those in Zimbabwe,  Zambia, and Pakistan, where thousands of typhoid cases have been reported. Without treatment, typhoid can cause serious short- and long- term complications, and even lead to death. While antibiotic treatment has greatly improved outcomes in typhoid patients, the effectiveness of antibiotics is becoming increasingly limited. The World Health Organization (WHO) has called antibiotic resistance one of the biggest threats to global health today, and treating typhoid is no exception. Drug and multi-drug resistant typhoid has been increasingly reported in LMICs in Southeast Asia and sub-Saharan Africa where typhoid burdens are highest, and treating drug-resistant typhoid may become prohibitively expensive. As global experts met this week at the International Caparica Conference in Antibiotic Resistance to discuss ways to address this growing issue, I reflected on ways that we can combat this looming threat for typhoid: 1. We need to accelerate the introduction of typhoid vaccines alongside proven water, sanitation, and hygiene (WASH) interventions. Just as we know how to treat typhoid, we also know how to prevent it: WASH precautions are key. However, given the significant burden of typhoid among hard-to-reach populations where WASH progress may be slow, we need an integrated approach to prevention that includes vaccines. Currently, two vaccines are globally available and are effective in preventing typhoid—an oral live attenuated vaccine and an injectable Vi capsular polysaccharide vaccine. In 2008, WHO recommended that both vaccines can be used during outbreaks and in endemic areas, but uptake has been low and neither are used routinely. Newer typhoid conjugate vaccines (TCVs) have the potential to overcome the shortcomings of the current vaccines by allowing for longer-lasting protection, fewer doses, and greater suitability for children younger than two years old in routine childhood immunization programs. The Typhoid Vaccine Acceleration Consortium (TyVAC), a partnership between the Center for Vaccine Development at the University of Maryland School of Medicine, the Oxford Vaccine Group at the University of Oxford, and PATH, an international nonprofit, is committed to ensuring that prevention and control of typhoid is a global health priority. We work with local and global partners to accelerate the introduction of TCVs in LMICs as part of an integrated prevention strategy. 2. We need research and development to advance the typhoid vaccine, drug, and diagnostics pipeline to prevent, accurately diagnose, and treat typhoid. One of the challenges of typhoid is that an infected person presents with symptoms that are often mistaken for other diseases, which leads to frequent misdiagnoses. Current diagnostics require blood or bone marrow and a lab to analyze the results, which is not feasible for many low-resource health facilities. Knowing that a patient has confirmed typhoid allows the physician to provide the proper course of treatment and helps combat antibiotic misuse. A robust vaccine and drug pipeline will help ensure that we continue to have a range of prevention and treatment tools at our disposal for typhoid. There are currently several TCVs in various stages of development. New vaccines provide a mechanism for protection against typhoid that can avert cases that may be drug resistant. As more vaccines and drugs become available, access improves and costs can come down due to healthy market competition. The time is now for us to #TakeonTyphoid. We cannot afford to risk typhoid becoming untreatable—not when we can strengthen prevention through immunization with TCVs and improvements in WASH.

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. CRISPR-cas9, a revolutionary gene editing tool, has been hailed a breakthrough device for microbiologists and geneticists—but not without certain reservations. In a study recently published in Nature, researchers attempting to target and edit genetic blindness in mice analyzed nucleotides—the single-unit building blocks for DNA—in the edited and control mice in order to evaluate success of the tool. CRISPR successfully targeted the alleles—or mutated nucleotides—causing blindness in the mice, but the editing also caused 1,600 off-target, unpredicted mutations, including 100 “large changes” in the DNA structure. This is important because single-nucleotide mutations are associated with many diseases, such as sickle-cell anemia, Huntington's disease, cystic fibrosis, and more. The researchers stressed that more needs to be done to study off-target mutations before CRISPR can be considered risk-free, but that the outlook for the tool is still positive, as any scientific tool has side effects. The science behind creating an effective vaccine that is capable of completely eradicating a disease is complex and hard-won. The only vaccine that has been used to successfully eradicate a disease in humans is the smallpox vaccine. Edward Jenner used cowpox, a similar but much less dangerous bovine variation of the disease, to create a successful vaccine against smallpox—and now scientists are going back to that methodology in an attempt to eradicate malaria. Scientists plan to genetically modify a rodent-variation of the malaria parasite to then use on healthy human volunteers. The hope is that the variation will result in a protective response in humans. The first phase of trials will begin in 2018 and will involve studying initial protection against the disease, with future phases focusing on continued efficacy of the vaccine. Motivated by a lack of awareness and funding for tuberculosis (TB), Médecins Sans Frontières, or Doctors Without Borders, launched a clinical trial, entitled  TB PRACTECAL, aimed at finding a new, improved treatment for drug-resistant TB. The trial, which officially launched in January 2017, is testing an innovative combination of TB drugs that will only need to be taken for six months. Current treatments for drug-resistant TB are physically and emotionally arduous, painful, and only successful about 50 percent of the time, which is why shorted, improved treatment regimens are needed. The first set of trial results is expected to be released within two years with final results within four. If successful, the organization hopes the new treatment will be rolled out in countries around the world and mark an important step forward in combatting the global epidemic.