‘The specificity of the Dexact-f test to rule out infectious focus in the bowel in over 92 per cent’

Tell us about your research in the arena of infectious diseases

Dr Fariba Nayeri

A large amount of cases presented to the doctors are either directly related to the field or in urgent need of consultation with an infectious disease specialist. Chronic infections prevent healing and cause complications that in many cases lead to unnecessary invasive interventions. The goal of our research has been to investigate the true cause and achieve healing of diseases.

Since 1999, we have studied the presence and biological activity of cytokines such as thehepatocyte growth factor (HGF) in blood and locally at the site of injuries caused by infection. We tried to develop reliable and reproducible methods for determination and evaluation of cytokine.

HGF is a protein produced by neighbour cells to heal injured organ cells. This protein is a potent healing factor which helps in the healing of injuries by at least three mechanisms :

• The healthy tissue cells increase in number (mitogen effects)
• The produced cells go to the injured area (motogen effect)
• The injured tissue grows back to the original healthy form (morphogen effect)

We found that the amount of HGF increased after all sorts of injuries, acute as well as chronic. However the acute injuries healed as soon as the infectious agent was eliminated. The chronic injuries on the other hand did not heal. Chronic ulcers are examples of chronic injuries that are very difficult to treat. We observed thatthe application of HGF to chronic injuries sometimes caused rapid healing. In some other cases, no positive effect was observed.

During the past ten years we have tried to find answer to the following questions:

• Why don’t chronic injuries heal?
• The concentration of HGF in the secretion from chronic injury is even higher than in acute injuries. Then why did application of HGF cause healing in some chronic injuries but not in all injuries?
• What are the properties that differentiate between the HGF produced during acute injuries and chronic injuries?
• Are there some infectious agents that are important in the chronicity of injuries?
• A chronic injury is always colonised with several bacteria. How can we recognise the responsible bacteria?
• Besides antibiotics, what other manoeuvres can be used to get rid of infection?

The summary of results achieved from the investigations so far is that:

• Changes in the shape of HGF (configuration) might cause differences in binding this cytokine to the receptors and thereby in the activity of protein in the body
• Some bacterial agents might cause changes in the configuration of HGF
• Inactive HGF does not bind to the extracellular matrix and cannot interact with the high affinity receptor on cell membrane
• Bacteria responsible for injuries produce peptides that are similar to the human body and hide from the immune responses (mimicry peptides)
• By production of antibodies in human cell cultures we can recognise such mimicry peptides
• A combination of effective antibiotics and biologically active HGF with high affinity to the extracellular matrix might treat chronic injuries rapidly
• Characterisation of biologically active HGF might be used to differentiate between acute and chronic injuries in body fluids

Based on the achieved results we have developed rapid tests to recognise the site and severity of infection.

You have developed Dexact-F, a strip to diagnose diarhhoea? What are its benefits, especially for a country like India?

Diarrhoea is a common symptom of several diseases, and a well-known cause of morbidity and mortality in the world. The major cause of diarrhoea is infection and therefore in order to avoid devastating complications, numerous cases are treated blindly by antibiotics. This has been an important cause of resistance development in bowel bacterial flora.

The conventional diagnostic routines in diarrhoea are stool direct microscopy, stool cultures and antigen detection methods in some medical centres. Due to vast antibiotic consumption and susceptibility of common causes of infectious gastroenteritis such as salmonella to antibiotics, the sensitivity of stool cultures are very low. Direct stool microscopy is a valuable method for diagnosis of parasites but cannot differentiate between infectious and non-infectious gastroenteritis.

Dexact-f is a marker of acute inflammation and the severity of inflammation. The specificity of the test to rule out infectious focus in the bowel in over 92 per cent and the sensitivity to diagnose a bacterial infection in the bowel is >92 per cent as long as inflammation causes injury. Therefore, during viral gastroenteritis the test turns to negative within 72 hours after the debut of infection. In cases with inflammation caused by parasites, positive test might be observed in acute phase of disease. The test is negative in carriers.

During the study of faeces samples with Dexact-f in Sweden, Egypt and India we have found that the test was positive in 20-30 per cent of cases with diarrhoea. Therefore, we hope that Dexact-f, as a complementary diagnostic tool to direct microscopy, might help to decrease antibiotic consumption in at least 50 per cent of cases and to differentiate the cases of acute inflammation in bowels that are in need of immediate care, such as during sepsis with systemic inflammatory response syndrome (SIRS).

Are you working on developing similar solutions for other infectious diseases as well?

Our proposed solution for rapid diagnostic of infectious focus is based on the tissue responses to the infection. We intend to recognise and determine such responses by means of rapid tests. The value of such an approach is that the physician is not bound to previous antibiotic consumption, poor sensitivity of cultures and too high sensitivity of PCR-based methods to set diagnosis. The tissue response is the valid answer of the body to the injury that can be determined and monitored.

We develop diagnostic and monitoring markers for diagnosis of bacterial infection in sterile samples.

We also develop high specific antibodies for detection of microbial antigens such as mycobacterium tuberculosis in blood samples.

What are the three important things that need to be done for curbing the growing incidences of infectious diseases?

The immediate measures needed are as follows:

• Promoting public as well as professional awareness
• Research and development of reliable and available diagnostic tools
• Decreasing antibiotic consumption and applying focused treatment

Tell us about the purpose of your visit to India?

As a researching doctor, I am keen and curious to find out and learn about the clinical practices and traditions in India and to contribute to the outline of future medical services in this country. Furthermore, I was very interested to meet and get acquainted with colleagues and medical staff.

What are the lessons that Sweden and India can learn from each other to improve their respective healthcare sectors?

Hopefully, the Swedish doctors can learn about the work load, burden from the large number of patients that Indian doctors are responsible for and get insights into the value of patient contact, viewing the patient as a whole. Swedish doctors may be the models in restrictive prescription and intensive follow-ups.

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