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Determining The Difference Between Viral And Bacterial Infection

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By Dr. Peggy Huang, Protein Chemist

IFA staining of specific C. Pneumonia proteins in host cell. IFA staining of specific RSV proteins on surface of host cell.

Being the mother of a young child, I am often faced with determining the difference between viral and bacterial infections when my son gets a fever. Maybe I’m a bit paranoid due to my experience in the biotech industry, but I’ve always followed the guidepost of “better safe than sorry.” Unless it’s something obvious, like a sore throat or a spell of the flu in wintertime, I’ve only verified cases of a viral infection when prescribed antibiotics were ineffective. This often leads to a hefty increase in the dosage of antibiotics.

Unnecessary use of antibiotics for viral infection

Increased antibiotics dosages bring along an increased drug-resistance in bacteria. Unnecessary use of antibiotics has become a growing hot topic in the medical world, one which continues to give rise to drug-resistant germs.

The CDC recently issued an urgent alert for some drug-resistant superbugs that were estimated to cause 23,000 deaths each year.1 This illustrates the dire importance of avoiding the overuse of antibiotics. Antibiotics not only kill bad bacteria, but also those good ones that humans need for natural functions, like digestion.

Progress in determining the difference between viral and bacterial infection

But how do you clearly distinguish between a viral and bacterial infection? The major benefit of early detection of any viral infection is that it enables treatment to be more effective while suppressing the virus from continuing to spread, such as the deadly SARS and MERS viruses now sweeping across the Middle East and parts of Europe. Many researchers are attacking this problem with various approaches.

Antibody based testing

Current tests use antibodies to recognize flu virus surface antigens – Hemagglutinin (H) and Neuraminidase (N) – two major surface proteins that help classify different Influenza Virus types (such as H1N1). Although these tests could produce results in as little as fifteen minutes, there are drawbacks: the high false negative rate and high cost. The CDC recommends a viral culture that takes 3 to 10 days and can help to confirm a viral infection.

Utilizing Carbohydrates in testing

A new report released this month from Georgia State University and the University of Cincinnati utilizes carbohydrates instead of antibodies to capture influenza antigens, showing quicker results with greater reliability and lower costs.

Innovation using host immune system response

Instead of detecting the existence of viral or bacterial antigens, which requires a strong knowledge of the antigen species, another new approach in distinguishing viral versus bacterial infections is through the detection of host immune responses. This concept is based on the recent discovery that the human immune system responds differently to viral and bacterial infections, activating different sets of genes and proteins. These subtle changes at the molecular level, or the genomic fingerprint, occur before a majority of symptoms develop.

DNA chip technology

In a recent study, the Storch Group from Washington University in St. Louis used a microarray (also referred to as a DNA chip) to identify different gene expressions in white blood cells, and found a distinctive signature pattern between viral and bacterial infections.2 The study managed to help distinguish viral and bacterial infections in thirty children in the age range of 2 months to 3 years old. The children had symptoms of fever, but no other obvious symptoms like coughing or diarrhea. Blood tests were taken from healthy controls and children who tested positive for Adenovirus, Human Herpesvirus 6, or acute bacterial infections. The results concluded that an IFN signaling pathway is uniquely active for viral infections, while an integrin signaling pathway is uniquely active for a bacterial infection. It is also worth noting that the same study revealed that an elevated white blood cell count is not a reliable indicator for a bacterial infection. Elevated white blood cell levels were also observed in a significant number of viral infections.

RT-PCR screening method

Using similar genomic fingerprint data, a study published this month by the Zaas Group from Duke University brought this method one step closer to diagnostic use.3 These experimental tests could eventually help physicians better diagnose not only viral versus bacterial threats, but also assist in screening for new viral threats like MERS or Dengue Fever. The study used RT-PCR to test blood samples of 102 adults admitted to the ER with a fever, and 41 healthy individuals to track the signature gene expression for viral infections. After 12 hours of testing, the genomic data translated into an 89% accuracy rating in differentiating those who had a virus, and those who didn’t. Improvements and modifications still need to be made to the testing process, as the 12 hour testing period is still too long to effectively alert real patients in time to seek proactive treatment for infections. Perfecting the test, however, will serve as a promising start to reducing the overuse of antibiotics.

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The need for even quicker results

A recent story claims that 20% of doctors in the US misdiagnose fatal illnesses,4 meaning that millions of sick people are receiving the wrong treatment for their symptoms (this is a less than stellar number considering that the US is the richest country in the world and 1/7 of our economy relies on people getting sick and waiting in long lines at the pharmacy to fill prescriptions). Testing for an illness is often administered based on a doctor’s assessment of patient symptoms and conditions, and many of the quick in-office testing methods are not as comprehensive and often miss infections. When symptoms alone fail to aid a diagnosis, doctors are left with no choice but to test their suspicions based merely on a patient’s history and symptoms, as well as the current medical trends (a high fever in the middle of winter will often lead to a test for Influenza virus).

In the long run, more efficient testing methods for viral and bacterial infections will only help improve the medical community as a whole, and give sick people a better chance to overcome illness. Of course the best way to fight any infection is to not get sick at all. As winter approaches and every gloomy day becomes a snow-fearing frenzy, it’s that time of year again for flu shots and practicing good hand hygiene. As the medical community continues to seek improvements for diagnostic methods, the rest of us can only wait and see if the viral versus bacterial challenge will be conquered sooner rather than later.

 
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References:

  1. Antibiotics Resistance Report from CDC https://www.cdc.gov/drugresistance/biggest-threats.html
  2. Hu, X., Yu, J., Crosby, S., and Storch, G. (2013) Gene expression profiles in febrile children with defined viral and bacterial infection. PNAS, 110 (31) 12792-12797; doi:10.1073/pnas.1302968110
  3. Zaas, AK. et al (2013) A Host-Based RT-PCR Gene Expression Signature to Identify Acute Respiratory Viral Infection. Science Translational Medicine , 5:203, pp203ra126; doi: 10.1126/scitranslmed.3006280
  4. Graber, M. (2013) The incidence of diagnostic error in medicine. Published online 2013 Jun 15. doi: 10.1136/bmjqs-2012-001615