Once upon a time, the best way to prevent and eliminate a food- and water-borne disease like typhoid fever was by improving sanitation and hygiene. Today, however, despite decades of progress with dramatic reductions in industrialized countries, mortality rates of typhoid have stagnated, even in countries with almost universal access to clean water. And now, a century after Irish cook Mary Mallon was condemned to spend the remaining 23 years of her life locked up in quarantine for unwittingly triggering a major outbreak in New York City — an act that earned her the nickname “Typhoid Mary” — we could once again start to see a resurgence of this disease. Blame it on growing resistance of the bacteria that cause the disease, Salmonella typhi, to antibiotics. It’s part of the growing problem known as antimicrobial resistance.
Until relatively recently, antibiotics were a major part of the solution in the fight against typhoid fever. Their introduction dramatically reduced the death rate from one death in every five cases to one death in every hundred cases. But through the widespread overuse and misuse of antibiotics, the typhoid-causing pathogen has developed resistance to multiple drugs. It is now one of biggest drivers of all drug resistance in Southeast Asia and probably in other regions as well. Not only does this mean that we could see the number of deaths from typhoid fever once again start to rise, but it also has implications for the spread of other drug-resistant pathogens, posing major regional and transcontinental threats.
In Karachi, Pakistan, antibiotic resistance is increasing by 30 percent per year. If this trend continues, by 2020 all cases of typhoid in Karachi would be resistant to multiple drugs. This problem doesn’t affect only the poorest countries. Thailand, which has a gross national income per capita nearly three times higher than Pakistan, and almost all of whose citizens have access to clean drinking water, still has persistent patterns of typhoid, with more than 1,000 deaths a year.
The solution to this problem is to prevent typhoid fever in the first place. Vaccination can do that. But even though a typhoid vaccine has been available for more than a century, and even though typhoid vaccination has been recommended by the World Health Organization for endemic countries since 1999, the existing vaccine is not a great one and its use has been extremely limited amongst high-risk populations. That should and must change now that a new vaccine will soon be available.
The typhoid conjugate vaccine (TCV) differs from previous ones in several ways. One is that it is more effective at preventing the disease than its predecessors. It is also longer lasting, providing protection for at least five years, and possibly longer, compared to just two years for earlier typhoid vaccines. Perhaps most important, it is also the first vaccine that can be given to children under the age of 2. That alone makes it a game-changer, because one of the main barriers to controlling typhoid has been the availability of a vaccine that is effective in young children.
If a vaccine can’t be given to young children, it can’t be included as part of existing childhood vaccination schedules, making it difficult and expensive to deploy. That means TCV should make it possible to protect more people, including a particularly vulnerable part of the population. About 8 percent of all typhoid deaths occur in children under age 2. Given that there are around 12 million typhoid fever cases globally a year, resulting in up to 130,000 deaths, the proportion of deaths under age 2 alone works out as more than the entire death toll of the recent Ebola epidemic in West Africa.
All of this makes TCV one of the most widely anticipated vaccines for years. With several other TCVs in development, the first is expected to be pre-qualified by the WHO before the end of the year, meaning it has been assessed in terms quality, safety, and efficacy, and also approved to be made available through United Nations agencies, such as UNICEF. This gives my organization, Gavi, the Vaccine Alliance, a green light to help make it available to the world’s poorest countries, which may not otherwise be able to afford the vaccine on the open market. The Gavi board voted Thursday to initially provide $85 million to help roll out the vaccine over the next few years.
Demand for the vaccine is expected to be high. Not just because TCV should save three lives for every 10,000 doses administered, but also because of the significant role it will play in reducing the growing threats posed by antimicrobial resistance, and the associated economic burden it brings. In Pakistan, for example, antibiotic resistance leads to longer hospital stays and more expensive courses of antibiotics as first-line drugs prove ineffective.
Compounding the issue is the fact that typhoid can be difficult to diagnose. Symptoms often get mistaken for other febrile diseases, such as malaria, leading to the wrong drugs being administered, with disastrous results.
It’s still not clear what the broader global impact of drug-resistant typhoid is likely to be on the spread of antimicrobial resistance in other pathogens. But what is clear is that typhoid infection is now playing a central role in the rise of antibiotic-resistant bacteria around the world. With an estimated 50 million doses of antibiotics prescribed for typhoid every year, one solution is simple: prevent the disease in the first place through vaccination and continued improvements in water and sanitation.
Seth Berkley, M.D., is CEO of Gavi, the Vaccine Alliance.
