For many years, researchers have subscribed to the dogma that bacteria cannot be whole-genome sequenced in Africa. Danish researchers have overturned this dogma and propose a new direction in healthcare that may significantly improve public health in African countries.
Imagine being infected by some exotic bacterium lurking mysteriously in your lunch. Fortunately, you live in Denmark, and a doctor can send a blood sample to a laboratory and find out a few days later which bacterium has caught you. Then the doctor just chooses the right treatment to make you well again.
Then imagine living in a small town in the middle of Africa. The situation is very different, because no one has either the knowledge or the equipment to determine which bacterium has infected you. Finding out whether you have a Salmonella infection, for example, can take several weeks. For local inhabitants in Africa, waiting can be painful and in some cases fatal.
However, good news is on the way. Danish researchers are the first globally to show that minimal investment in a single machine can replace equipment worth millions and decades of expert knowledge. The machine can do everything in much less than half the time. This works in Denmark and can also work in Africa.
“We have shown that healthcare professionals in Africa can be trained to use a whole-genome sequencer costing 500,000 kroner. This means that the waiting time to identify a pathogenic bacterium can be cut from a couple of weeks to 48 hours. This can massively improve public health in Africa,” explains the researcher behind the new study, Frank Møller Aarestrup, Professor, National Food Institute, Technical University of Denmark.
He and his colleagues have published their research results in the European Journal of Clinical Microbiology & Infectious Diseases.
Advanced equipment can definitely be used in Africa
Understanding the new results is not especially complicated. The researchers installed a whole-genome sequencer in a hospital in Moshi, Tanzania and trained healthcare professionals to use and service it.
The aim was to see whether the personnel available could operate the sequencer and get it to function under local conditions.
They could. No ifs, ands or buts!
The sequencer enabled local healthcare professionals to identify the bacteria from infected people in just 48 hours, much more rapidly than previously.
“It may sound easy, but many researchers did not believe that this could be done in Africa, which in many ways still has very underdeveloped healthcare systems. I often meet researchers who condescendingly do not think that local personnel in Africa can administer this type of machine over the long term, but they can,” explains Frank Møller Aarestrup.
Denmark is still using old equipment
High-income countries differ enormously from low- and middle-income countries in the normal procedures for identifying harmful bacteria.
A country like Denmark has accumulated a well-functioning arsenal of laboratory equipment over decades, enabling bacteria to be identified in many different ways. Traditionally, Denmark has used the Petri dish, growth media, microscopes and expert knowledge, but today whole-genome sequencers are used to perform most of the analysis based on the DNA from a bacterium. The results can then be used to determine the species.
Low- and middle-income countries that do not have access to laboratory equipment costing billions have two options:
• invest in the traditional equipment and develop the necessary expertise; or
• invest in new equipment.
“Conservatism is rife in this field, and even in Denmark we still use some old equipment because we have a tradition of doing so. However, I do not think that countries in Africa, for example, should take this path. Instead, these countries should use the new methods and learn to operate the equipment correctly,” says Frank Møller Aarestrup.
Database matches DNA against known bacteria species
Whole-genome sequencers have many advantages.
• The sequencer functions very simply. DNA is extracted from a bacterium and fed into the sequencer, which then spits out a long DNA sequence of about 7 billion letters. This information is unusable in its raw form, but comparing it with a database containing the DNA sequences for all known bacteria immediately reveals the identity of the bacterium being tested.
• In addition, the sequencer can detect small differences between individual bacteria, enabling healthcare personnel to determine whether the bacterium infecting you is the same as that infecting your neighbour. This enables researchers to follow the transmission of the infection and identify the source.
• Doctors can also match bacteria with known types of multidrug-resistant bacteria enabling them to prescribe the right type of antibiotics.
“Whole-genome sequencing enables hospitals to diagnose the cause of an infection much more rapidly and precisely. This can significantly reduce the treatment time in places where this currently takes a long time,” explains Frank Møller Aarestrup.
New knowledge causes new headaches
Nevertheless, not everything in Moshi is perfect.
Doctors can now use a whole-genome sequencer to determine that many infections spread within hospitals, and this obligates them to act. But they do not know how.
“The problem is that doctors now have some information that they would rather not have, because they do not know how to stop transmission. However, the research project is not focusing on this now, but this is a separate problem that needs to be addressed,” says Frank Møller Aarestrup.
Danish Veterinary and Food Administration uses only sequencing
Previously, Frank Møller Aarestrup’s research group conducted another study showing the power of whole-genome sequencing in identifying infectious bacteria.
Some years ago, they evaluated the potential of whole-genome sequencers for identifying foodborne bacteria. The study compared the performance of a sequencer with the performance of traditional methods; the sequencer identified a bacterium a whole week sooner than the traditional methods and was even cheaper.
“The result was that the Danish Veterinary and Food Administration uses only sequencing to identify bacteria today. Hospitals in Africa should also do this, and we have shown that this is feasible,” concludes Frank Møller Aarestrup.
“Molecular epidemiology of virulence and antimicrobial resistance determinants in Klebsiella pneumoniae from hospitalised patients in Kilimanjaro, Tanzania” has been published in the European Journal of Clinical Microbiology & Infectious Diseases. In 2016, the Novo Nordisk Foundation awarded a Challenge Programme grant of DKK 60 million to Frank Møller Aarestrup for the project Global Surveillance of Antimicrobial Resistance.
