Typhus has mutated to beat antibiotics. Science is learning to defeat these strains

Do you remember the story of Typhoid Mary, the cook who spread typhus to as many as 100 people in the early 1900s even though she herself showed no symptoms? She was confined to solitary confinement for 26 years because, at the time, there were no treatments that could cure this so-called “healthy carrier”.

We have since developed powerful antibiotics that could have wiped out Mary’s typhus and have been used to successfully treat many millions of people with the disease.

But the ancient typhus disease has adapted to modern times. New antibiotic-resistant strains are on the rise, fueling outbreaks around the world and making up a larger percentage of the annual toll of 10-20 million cases and 100,000 deaths. And now science is fighting by stepping up vaccination campaigns and finding more efficient ways to find cases of typhus.

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/ New York Public Library

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The New York Public Library

“Typhoid Mary”, the cook believed to have infected about 100 people with the disease, as depicted in the New York American, June 1909.

Typhus superbugs made their debut around 1950

Some things about typhus are unchanged from the days of Typhoid Mary. The disease is caused by bacteria Salmonella enterica Typhi serotype (S. Tifi). 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 cause internal bleeding and death.

Antibiotic-resistant typhus first appeared on the scene around 1950. Since then, almost every time a new antibiotic with the potential to cure typhus is developed, a new strain has emerged that can beat it.

“It’s all this back and forth. We develop new drugs, typhus becomes resistant,” says Dr. Jason Andrews, associate professor of infectious diseases at Stanford University. “It has happened over and over for 70 years now.”

The worst strain is called XDR, short for broadly drug resistant. It first emerged in Pakistan in 2016 and became the dominant strain in the country in 2019. It is also widespread in other countries, according to research published in June in The Microbe Lancet. This spread is what worries scientists like Andrews, an author of the article. This is because there is only one oral antibiotic that can cure XDR typhus: azithromycin, which was approved for medical use in 1988 and is one of the most commonly prescribed antibiotics on the market. But researchers fear that widespread use of azithromycin could lead to XDR becoming resistant to the drug.

A new vaccine could be the key to stopping XDR typhus

So how can you stop XDR? A relatively new weapon in the typhus arsenal is a vaccine that the World Health Organization recommended for use in 2018. It’s called Typbar and combines two types of antigens – parts of the 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 studies for the vaccine were published, each of which demonstrated approximately 80% effectiveness in preventing typhoid infection among approximately 90,000 vaccinated children in areas where XDR typhoid is rampant.

And there has been even better news since the vaccine has been widely used not only in Pakistan but also in Liberia, Zimbabwe and Nepal.

Now that the vaccine is no longer being tested, more than 90,000 people have been vaccinated and the preliminary results surpass the trial data. “The vaccination campaign in Pakistan was about 95% effective. [at preventing typhoid infection]”says Dr. Kathy Neuzil, director of the Center for Vaccine Development and Global Health at the University of Maryland.

But even though the vaccine has reduced the number of cases, it hasn’t exactly kayoed XDR. The vaccine has not yet been able to dent the rate of XDR infections in Pakistan. “Before vaccination, 60 to 70% of typhoid infections [in Pakistan] were from XDR and it continues to be so even after the vaccination campaign, “says Dr Farah Qamar of Aga Khan University, a Pakistani researcher who has been working on typhus for over a decade. Qamar says she would have expected the ‘XDR began to disappear because fewer cases mean fewer antibiotics are prescribed, but that doesn’t seem to have happened.

To slow the spread of typhus, we first need to find out where it is

So, what is the problem? One problem is that the vaccine supply is limited and it’s not easy to figure out where it will do more. Ideally, the doses would be sent to the regions with the highest number of XDR cases. However, current tools for detecting typhus are not good enough for detecting such hot spots.

“The big challenge with typhus is that it’s very difficult to diagnose, so we know it’s there, but we don’t really know how much of it there is,” says Dr. Kristen Aiemjoy, professor of epidemiology at UC Davis. “Blood culture is the diagnostic gold standard for typhus and it’s actually not that great. It only has a sensitivity of 60% – out of 100 true cases, you’re missing 40. Plus, it’s expensive and typically only available in hospitals. reference and in the capitals “.

To better count typhus cases, scientists have developed a new tool, also reported in The Microbe Lancet in June, a drop of blood from a fingertip is enough to find the disease. Even if the blood was drawn for other reasons, such as searching for COVID cases, the tool can still be used to detect typhus. The hope is that this method will help determine what researchers call the “strength of the infection” – the rate at which typhus is spreading across a country.

“This is the metric that is actually much more relevant to public health planning, because it tells you where cases are likely to increase. This can be used to justify where to throw the vaccine,” says Aiemjoy.

Doctors Without Borders has helped introduce this tool in countries that probably have a lot of typhus but little data on its prevalence, such as South Sudan.

/ Jason Andrews

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Jason Andrews

Wastewater flowing alongside households in Vellore, India is open. Poor sanitation practices can lead to a rapid spread of typhus, which can be contracted from contact with infected feces.

To get rid of typhus completely, however, it is necessary to address the source of the outbreaks: water and food contaminated with infected fecal matter. “There is a real need for improved water and sanitation, because unless that happens, we won’t be able to control typhus or other similar diseases,” says Qamar.

This has been done before. “Typhus was a leading cause of morbidity in the United States in 19th century then it was nearly eliminated city after city over a 10-year period, “says Andrews. Simple measures such as connecting homes to proper sewage systems and clean water lines were all it took.

The infrastructure obviously cannot be improved overnight. Meanwhile, Andrews is optimistic that with better diagnostic data and effective vaccines, antibiotic-resistant strains of typhus will be prevented from spreading further.

“Vaccines are not enough to eliminate typhus as we know it, but hopefully they can bring down the incidence [of typhoid] at more manageable levels as we seek to institute more permanent and effective measures for elimination, such as clean water and sanitation. ”

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