Do you remember the story of Typhoid Marie – the cook who spread typhoid to as many as 100 people in the early 1900s when she herself had no symptoms? She was confined to solitary confinement for 26 years because, at the time, no treatment could cure this so-called “healthy carrier”.
Since then, we have developed powerful antibiotics that could have wiped out Mary’s typhoid and have been used to successfully treat millions of people with the disease.
But the ancient disease of typhoid has adapted to modern times. New antibiotic-resistant strains are on the rise, fueling epidemics across the world and accounting for a larger percentage of the annual toll of 10-20 million cases and 100,000 deaths. And now science is fighting back by stepping up vaccination campaigns and finding more effective ways to detect cases of typhoid.
Typhoid superbugs first appeared around 1950
Some things about typhoid are unchanged from the days of Typhoid Mary. The disease is caused by bacteria Salmonella enterica serotype Typhi (S typhi). This strain of bacteria only infects humans – as far as we know – and is spread through contact with infected feces. Symptoms include high fever, fatigue, and digestive problems, which can eventually lead to internal bleeding and death.
Antibiotic-resistant typhoid first emerged around 1950. Since then, almost every time a new antibiotic with the potential to cure typhoid is developed, a new strain emerges that can defeat it.
“It’s this back and forth. We develop new drugs, typhoid becomes resistant,” explains Dr Jason Andrews, associate professor of infectious diseases at Stanford University. “It’s just happened over and over again, now for 70 years.”
The worst strain is called XDR – short for highly drug resistant. It first appeared in Pakistan in 2016 and in 2019 became the dominant strain in the country. It has also spread to other countries, according to a study published in June in The lancet microbe. This spread is what worries scientists like Andrews, an author of the paper. This is because there is only one oral antibiotic that can cure typhoid XDR: azithromycin, which was approved for medical use in 1988 and is one of the most effective. commonly prescribed antibiotics on the market. But researchers fear that widespread use of azithromycin could lead XDR to become resistant to the drug.
A new vaccine could be the key to stopping typhoid XDR
So how can XDR be stopped? A relatively new weapon in the typhoid arsenal is a vaccine recommended for use by the World Health Organization in 2018. It’s called Typbar and it combines two types of antigens – parts of bacteria that the human immune system can recognize – to stimulate an immune response. and prevent typhoid infection, even if it is resistant to antibiotics.
Last year the results of Three trials for the vaccine have been published, each showing around 80% efficacy in preventing typhoid infection in around 90,000 vaccinated children in areas where XDR typhoid occurs.
And there was even more good news as the vaccine was widely used not only in Pakistan but also in Liberia, Zimbabwe and Nepal.
Now that the vaccine is no longer in trials, well over 90,000 people have been vaccinated and preliminary results exceed trial data. “The vaccination campaign in Pakistan was about 95% effective. [at preventing typhoid infection],” said Dr. Kathy Neuzildirector of the Center for Vaccine Development and Global Health at the University of Maryland.
But even though the vaccine brought down the number of cases, it wasn’t exactly successful in XDR. The vaccine has not yet been able to reduce the rate of XDR infections in Pakistan. “Before vaccination, 60 to 70% of typhoid infections [in Pakistan] came from XDR and this continues to be the case even after the vaccination campaign,” says Dr. Farah Qamar from the Aga Khan University, a Pakistani researcher who has been working on typhoid for more than a decade. Qamar says she would have expected XDR to start disappearing because fewer cases mean fewer antibiotics are prescribed, but that doesn’t seem to have happened.
To slow the spread of typhoid, we must first know where it is
So what is the problem? One of the problems is that the supply of vaccines is limited and it is not easy to determine where it will do the most good. In an ideal situation, doses would be sent to regions with the highest number of XDR cases. However, current typhoid detection tools are not good enough to identify these hotspots.
“The big challenge with typhoid is that it’s very hard to diagnose, so we know it’s there, but we don’t really know how many there are,” says Dr Kristen Aiemjoy, professor of epidemiology at UC Davis. “Blood culture is the go-to diagnosis for typhoid and it’s actually not that great. It only has 60% sensitivity – out of 100 real cases, you’re missing 40. On top of that , it is expensive and usually only available in referral hospitals and capital cities.
To better count typhoid cases, scientists have developed a new tool, also reported in The lancet microbe in June, it only takes a drop of blood from a finger prick to find the disease. Even if the blood was drawn for other reasons – like finding COVID cases – the tool can still be used to detect typhoid. The hope is that this method will help determine what the researchers call the “strength of infection” – how quickly typhoid is spreading in a country.
“It’s the metric that’s actually much more relevant for public health planning because it tells you where cases are likely to increase. It can be used to justify where to deploy the vaccine,” says Aiemjoy.
Doctors Without Borders has helped introduce this tool in countries that likely have a lot of typhoid but poor data on its prevalence, such as South Sudan.
However, to completely get rid of typhoid, you have to attack the source of the epidemics – water and food contaminated with infected feces. “There really is a need for improved water and sanitation because unless that happens we won’t be able to control typhoid or other similar diseases,” says Qamar.
It has already been done. “Typhoid was one of the leading causes of morbidity in the United States in the 19e century and then was almost eliminated city by city over a 10-year period,” says Andrews. Simple measures like connecting homes to proper sewage systems and clean water pipes were all it took.
Of course, infrastructure cannot be improved overnight. In the meantime, Andrews is optimistic that with better diagnostic data and effective vaccines, antibiotic-resistant strains of typhoid will be stopped from spreading further.
“Vaccines are not enough to eliminate typhoid as we know it, but hopefully they can reduce the incidence [of typhoid] to more manageable levels as we try to institute more permanent and effective disposal measures, such as clean water and sanitation.”
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