Newborns and the Microbiome

 Hypothetical Case Study: Atypical Pneumonia in 24-Year Old Student

Monica Edlauer

July 22, 2017

Sofia, a 24-year old acupuncture student, had just returned home to Boulder, CO from a semester-abroad in China. She had spent the 5-week program in the Guangdong Province at Clifford Hospital. While on the airplane back to Boulder, Colorado, she developed a dry cough and sore throat, feeling like she was coming down with a cold.  Sofia figured the strenuous work and travel of the semester had depleted her immune reserves and she would rebound with some self-care. But her symptoms seemed to get worse, even though she was taking self-prescribed Cold Snap and getting a fair amount of rest since she had returned. The school clinic at Southwest Acupuncture College was closed for break, so she made an appointment with her family naturopath. Luckily, her ND was able to get her into the office within a couple of days. 

After muscle-testing Sofia for influenza A and B, her naturopath sent her home with a box of Oscillococcinum with instructions to ingest an entire vial once every hour for the first 6 hours, and once every 3 hours thereafter until symptoms cleared. Surprisingly, Sofia felt worse the next day. Her fever was a full degree higher – now 102.2 – and she felt increasing chills and body aches, along with a pounding headache. Her roommate, a nursing student at a nearby community college, encouraged Sofia to pay a visit to the urgent care facility down the street.

By the time Sofia went to the urgent care, her symptoms were largely unchanged; her fever was 101.3, even though she had taken 200mg ibuprofen 90 minutes prior, and she was experiencing moderate dyspnea. A chest X-ray revealed small, bilateral patchy shadowing with interstitial infiltrates. Diagnosed with pneumonia, Sofia left the urgent care with a prescription for Azithromycin, which she filled immediately. 

After the five-day course of the antibiotic, Sofia still felt ill. She was starting to give up hope on both Eastern AND Western medicine, but decided to give allopathy one more chance, as her Medicaid would cover the office visits.  Although her fever had gone down to 99.8 for the last two days, her breathing remained labored, and she began suffering bouts of diarrhea.  Attributing the digestive symptoms to the antibiotics, Sofia started a course of probiotics recommended by the staff at Pharmaca. Already well into her second week of illness, Sofia called her primary care staff at People’s Clinic and was able to secure an appointment the following day. 

Because of Sofia’s history of travel outside of the country and failure to respond adequately to the Z-pack, her physician ordered a second X-ray and sputum Gram stain and culture. Sputum cultures were fixed in 95% ethanol overnight, then subjected to PAP (Papanicolaou) staining, a common technique utilized in cytopathology, which incorporates polychromatic dyes to differentiate various components of the cells (Giri, 2016).

Chest radiographs confirmed the presence of peripheral air-space opacities, and sputum samples reflected loose aggregates of macrophages exhibiting distinct cytoplasmic foaminess, vacuole formation, multinucleation and a ground glass appearance to the nuclei (Tse et al, 2004).

Sofia’s pathogen was difficult to identify for a variety of reasons. Her initial misdiagnosis by, first, her naturopath, and second, the urgent care facility, could have cost her life. The affected area appeared to be her respiratory system, but later symptomology including unabating fever, failure of initial antibiotic treatment, and emerging diarrhea could have been misleading.  Physically, Sofia was suffering from a cough, dyspnea, body aches, chills, headache, fever, and eventually diarrhea.  The chest X-ray indicates infiltrates and shadowing indicative of pneumonia.  Pneumonia could be viral or bacterial, but it typically relents to Azithromycin.  The fact that Sofia’s symptoms were not clearing up with the Z-pack was a red flag for her physician at People’s Clinic, as well as her prior travel to China, specifically Guangdong. 

There could have been several diagnoses, but the most likely was some sort of atypical pneumonia based on her symptomology.  Besides radiography, initial diagnostic testing could have included pulse oximetry, bacterial blood cultures, sputum tests, urinalysis, mycoplasma testing, rapid influenza diagnostic testing (not via muscle testing!), Legionella specimen, or even sputum smear for Pneumocystis jiroveci by silver stain (Prieser and Drosten, 2003). The second chest X-ray which showed peripheral air-space opacities could have indicated Mycoplasma, Chlamydia, Legionella, or viral pneumonia (Prieser and Drosten, 2003). The most definitive test for this particular pathogen was the sputum test run by the clinic. In addition, she could have run an RT-PCR (Reverse Transcriptase Polymerase Chain Reaction) assay to detect the particular gene expression of the viral RNA (CDC, 2005). Of course, the virus can only be viewed via electron microscope.

Final diagnosis of the virus that worsened Sofia's condition turned out to be SARS-Coronavirus (SARS-CoV), which originated and spread initially in the Guangdong Province in China. Negative-stain transmission electron microscopy reveals spherical to pleomorphic enveloped particles studded with spike glycoproteins (Tse et al, 2004).

Up until just weeks ago, no effective treatment for SARS-CoV had been developed or even studied.  Ribavirin, a nucleoside analog and broad-spectrum antiviral used concurrently with corticosteroids has been utilized with some success, although side-effects and lack of clinical trials resulted in much criticism (Preiser & Drosten, 2003). Just last year, genome identification of susceptibility loci had isolated surface vimentin as the critical cell entry site for the SARS-CoV (Yvonne Ting-Chun et al, 2016), and was a hopeful lead toward development of a more effective and specific antiviral medication. However, less than a month ago, reports of a nucleotide prodrug, GS-5734, which is undergoing clinical trials to treat Ebola, has proven to inhibit SARS-CoV and MERS-CoV, a slightly more contemporary, nearly identical virus (Sheahan et al, 2017). Not only did GS-5734 successfully inhibit SARS-CoV and multiple coronaviruses and zoonotic diseases including Marburg hemorrhagic fever, but it did not have any toxic effect on the host culture. This particular nucleotide analog prodrug works by blocking the viral RNA replication process (U.S. Army, 2015). Scientists postulate that this antiviral could be the key preventative mechanism in future coronavirus outbreaks, regardless of its genetic specificity (Sheahan et al, 2017). 

References

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Kightly, Russell.  (n.d.).  Sars Coronavirus virion.  Retrieved on July 21, 2017 from http://printed.scientific.graphics/featured/sars-coronavirus-russell-kightley.html

Preiser, W. & Drosten, C. (2003). Retrieved from http://www.sarsreference.com/ sarsref/virol.htm

SARS virion stain image. (2013). Retrieved on July 21, 2017 from http://www.nhs.uk/conditions/SARS/Pages/ Introduction.aspx

Schematic drawing of SARS coronavirus. (2007).  Retrieved on July 20, 2017 from http://www.sinobiologicalcdn.com/themes/sino/images/SARS.png

Severe Acute Respiratory Syndrome (SARS): Laboratory diagnostic tests. (2003). World Health Organization. Retrieved on July 8, 2017 from http://www.who.int/csr/sars/diagnostictests/en/

Sheahan, T., Sims, A., Graham, R., Menachery, V., Gralinski, L., Case, J., Leist, S., Pyrc, K., Feng, J., Trantcheva, I., Bannister, R., Park Y., Babusis, D., Clarke M., Mackman, R., Spahn, J., Palmiotti, C., Siegel, D., Ray A., Cihlar, T., Jordan, R., Denison, M., and Bari, R.  (2017).  Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Science Translational Medicine. 28 Jun 2017: Vol. 9, Issue 396, eaal3653. DOI: 10.1126/scitranslmed.aal3653

Tse, G. M. K., Hui, P.-K., Ma, T. K. F., Lo, A. W. I., To, K.-F., Chan, W. Y., … Ng, H.-K. (2004). Sputum cytology of patients with severe acute respiratory syndrome (SARS). Journal of Clinical Pathology, 57(3), 256–259. http://doi.org/10.1136/jcp.2003.012948

US Army Medical Research Institute of Infectious Diseases. (2015, October 9). Antiviral compound provides full protection from Ebola virus in nonhuman primates. ScienceDaily. Retrieved July 21, 2017 from www.sciencedaily.com/releases/2015/10/151009155415.htm