Scientists 'amazed' at spread of typhoid 'superbug' ...

“Antibiotic-resistant typhoid is spreading across Africa and Asia and poses a major global health threat,” BBC News reports.

Typhoid fever is a bacterial infection. If left untreated, it can lead to potentially fatal complications, such as internal bleeding.

Uncommon in the UK (there were 33 confirmed UK cases in the first quarter of 2015 and it is thought most of these were contracted abroad), it is more widespread in countries where there is poor sanitation and hygiene.

The headline is based on a study that looked at the genetics of the bacteria that causes typhoid fever, Salmonella typhi, to trace their origins.

The study analysed genetic data from almost 2,000 samples of Salmonella typhi collected between 1903 and 2013. It was looking for a strain called H58 that is often antibiotic-resistant. It found that this strain was likely to have originated in South Asia around the early 1990s, and has spread to other countries in Africa and Southeast Asia. It accounted for about 40% of samples collected each year. Over two-thirds of the H58 samples had genes that would allow them to be resistant to antibiotics.

It would be complacent to assume that this is just a problem for people in the developing world, as antibiotic resistance is a major threat facing human health worldwide. Studies such as this help researchers to identify and track how such bacteria spread. This may help them to use existing antibiotics more effectively, by identifying where specific types of resistance are common.

Where did the story come from?

The study was carried out by a large number of researchers from international institutions, including the Wellcome Trust Sanger Institute, in the UK. The researchers were also funded by a wide range of international organisations, including the Wellcome Trust and Novartis Vaccines Institute for Global Health.

The study was published in the peer-reviewed journal Nature Genetics.

The news sources cover this story reasonably. Some reporting implies that it is the H58 strain that is killing 200,000 people a year, but this study has not assessed this.

The 200,000 figure seems to be taken from information provided by the US’s Centers for Disease Control and Prevention (CDC), and is an estimate of all types of typhoid fever, not just the H58 strain.

What kind of research was this?

This was a genetic study looking at the origins and spread of the H58 strain of Salmonella typhi – the bacteria that causes typhoid fever. This strain is often found to be antibiotic-resistant.

The typhoid bacteria are spread by ingestion of infected faecal matter from a person with the disease. This means that it is a problem in countries where there is poor sanitation and hygiene. Typhoid fever is uncommon in the UK, and most cases in this country are people who have travelled to high-risk areas where the infection still occurs, including the Indian subcontinent, South and Southeast Asia, and Africa. The researchers say that 20-30 million cases of typhoid are estimated to occur each year worldwide.

Typhoid fever has been traditionally treated with the antibiotics chloramphenicol, ampicillin and trimethoprim-sulfamethoxazole. Since the 1970s, strains of typhoid have started to emerge that are resistant to these antibiotics (called multidrug-resistant strains). Different antibiotics, such as fluoroquinolones, have been used since the 1990s, but strains resistant to these antibiotics have been identified recently in Asia and Africa. One such strain, H58, is becoming more common, and was the focus of this study.

What did the research involve?

The researchers used genetic sequence data from 1,832 samples of Salmonella typhi bacteria collected across the world. They used this data to assess when the H58 strain (which has identifiable genetic characteristics) had arisen and how it had spread.

They first identified which of the samples belonged to the H58 strain, and in what year it was first identified. They also looked at what the proportion of samples collected in each year were of this strain, to see if it was becoming more common.

Over time, DNA accumulates changes, and the researchers used computer programmes to analyse the genetic changes present in each sample to identify how each strain is likely to be related to the others. By combining this information with the origin and year of each sample, the researchers developed an idea of how the strain had spread.

What were the basic results?

The researchers found that nearly half of their samples (47%) belonged to the H58 strain. The first sample identified as part of this strain was from Fiji in 1992, and continued to be identified up to the latest samples, from 2013. H58 strain samples were identified from 21 countries in Asia, Africa and Oceania, showing that it is now widespread. Overall, 68% of these H58 samples had genes that would allow them to be antibiotic-resistant.

There were some very genetically closely related samples found in different countries, suggesting that there was human transfer of the bacteria between these countries. Their genetic analyses suggested that the strain was initially located in South Asia, and then spread to Southeast Asia, western Asia and East Africa, as well as Fiji.

There was evidence of multiple transfers of the strain from Asia to Africa. The H58 strain accounted for 63% of samples from eastern and southern Africa. The analysis suggested that there had been a recent wave of transmission of the H58 strain from Kenya to Tanzania, and on to Malawi and South Africa. This had not previously been reported, and the researchers described it as an “ongoing epidemic of H58 typhoid across countries in eastern and southern Africa”.

Multidrug resistance was reported to be common among H58 samples from Southeast Asia in the 1990s and, more recently, samples from this region have acquired mutations which have made them less susceptible to fluoroquinolones. These have become more common in the area, and researchers suggested that this is due to the use of fluoroquinolones to treat typhoid fever over this period, leading to these resistant strains having a survival advantage.

In South Asia, there are lower rates of multidrug resistance in recent samples than in Southeast Asia. In Africa, most samples showed multidrug resistance to the older antibiotics, but not fluoroquinolones, as these are not frequently used there.

How did the researchers interpret the results?

The researchers say that their analysis is the first of its kind for the H58 typhoid strain, and that the spread of this strain “requires urgent international attention”. They say that their study “highlights the need for longstanding routine surveillance to capture epidemics and monitor changes in bacterial populations as a means to facilitate public health measures, such as the use of effective antimicrobials and the introduction of vaccine programs, to reduce the vast and neglected morbidity and mortality caused by typhoid”.

Conclusion

This study has provided information about the spread of a strain of typhoid called H58, which is commonly antibiotic-resistant, by looking at the genetics of samples collected between 1903 and 2013. It has shown that the strain was likely to have arisen in South Asia and then spread to Southeast Asia and Africa. The strain showed different patterns of antibiotic resistance in different regions – likely driven by different patterns in the use of antibiotics.

While this study has not estimated the number of cases or deaths worldwide attributable to this strain specifically, there are reported to be 20-30 million cases of typhoid fever globally each year.

The spread of antibiotic resistance is a major threat to human health, and studies like this can help us to monitor them and target treatment more effectively.