Pathogen Patient A


The following is a description of a patient that was presented in the New England Journal of Medicine, October 22, 2014 DOI: 10.1056/NEJMoa1411677.

The patient is a 36 year-old male who worked for WHO as an epidemiologist in Sierra Leone. Apparently, he contacted Ebola (EBOV) through a co-worker, with whom he shared an office for meetings and a restroom. The co-worker died 10 days before the onset of symptoms by the patient.

The 36-year-old male patient had malaise, headache, myalgias, and arthralgias on day 1 of the illness (August 18, 2014). Fever developed on day 2, and the patient was treated empirically for malaria. On days 2 through 6, he also received empirical antimicrobial therapy with ceftazidime. On day 6, he tested positive for EBOV.......Nausea, vomiting, abdominal pain, and nonbloody diarrhea developed on day 7.....supportive therapy with intravenous fluids was initiated and maintained until day 10, when he was transferred to Hamburg (Germany).

On admission to our facility, the patient was clinically stable, with an elevated temperature (38.4�C), but other vital signs were within normal limits. ....The patient was awake, alert, and fully oriented. Physical examination revealed signs of dehydration and diffuse abdominal tenderness. Rash was absent....

Ultrasonography of the abdomen revealed a complete collapse of the inferior vena cava, a paralytic ileus with pronounced edema of the small intestine and large intestinal wall, and distended intestinal loops. With the exception of enlarged mesenteric lymph nodes, all the other organs appeared normal. (paralytic ileus means lack of movement of the GI tract)

Below is a table with selected clinical tests. Day 10 is the first day in Hamburg.

Day normal 10 11 12 13 14 15 16 17
temperature 37 38.4 39.3 38.8 40.0 40.0 39.8 38.8 38.8
heart rate 60-90 96 92 80 140 170 160 140 150
respiratory rate (breaths/min) 12-14 ND ND ND ND 40 40 39 35
oxygen saturation (%) >95% 97 93 95 88 89 90 92 93
intravenous fluids (ml) (ECF vol = 14,000) 7850 13,175 11,675 9200 7510 13,734 7574 4418
diarrhea (ml) - 4400 8400 6850 4030 2230 950 500 --
hematocrit (%) males 39-49% 55.2 48.4 42.9 49.4 43.3 44.1 39.4 33.6
white cells (1000/mm3) 4.8-10.8 6.8 6.4 7.3 14.1 21.8 28.7 19.7 13.0
platelets (1000/mm3) 150-450 103 116 152 135 101 81 83 46
D-dimer (ng/ml) <500 33000 38000 38000 37000 35000 28000 24000 11000
C-reactive protein (mg/l) 0-5 11 13 23 43 59 123 127 65
lactate (mm/l) approx 1.5-2.0 1.8 2.7 1.5 2.8 6.5 9.3 1.7 1.1



QUESTION: Let's first look at his condition on arrival in Hamburg. Notice the hematocrit on day 10. Why is it abnormal in this way?

Answer

QUESTION:The inferior vena cava is a large vein attached to the heart. Veins are thin-walled. Why do you suppose they mention that it is collapsed?

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QUESTION: Severe edema is observed in the intestinal walls. What specific physiological factors account for this?

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QUESTION: What specific test above indicates that substantial amounts of TNF-alpha and IL-1 are being released due to the infection?

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Although not shown in the table above, the amount of viral RNA in the plasma was quite high on day 10, but in the ensuing days declined until it was essentially zero on day 17. Also, note in the table that the diarrhea decreased from over 8 liters a day to very little on day 17. Despite the steady decline in these data, notice the big changes occurring in some of the other values on about day 14 or 15. The authors point to peritonitis due to a seriously disrupted intestinal mucosa. (The peritoneum is the slippery membrane that lines the abdomen and covers the intestines. The mucosa of the intestines consists of the epithelium and some underlying tissue. Inflammation is always indicated by "-itis".)



QUESTION: What do you supposed is causing the big changes in the white blood cells and C-reactive protein?

Answer



The term sepsis refers to the presence of pathogenic microorganisms in the blood and implies a systemic inflammatory response. This is why the white blood cells and C-reactive protein are elevated.

Sepsis can cause several serious problems. One is difficulty in maintaining blood pressure. Vasodilation of small blood vessels occurs in inflammation. Since this is occuring systemically, blood is leaving the arterial system more rapidly than normal. This is why the heart must beat faster to maintain the blood pressure.



QUESTION: But do you see something in the clinical tests that indicate that septic shock is beginning? Recall that shock is inadequate perfusion (blood flow) to tissues.?

Answer



The patient also began to develop some serious respiratory problems, including at least partial collapse of the lungs.

"The respiratory status is further compromised by aspiration of blood from epistaxis...."



QUESTION: Epistaxis means nose bleeding. Which one of the clinical tests above explains this type of spontaneous hemorrhage? (This question and the next will be more clear after we cover blood clotting.)

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QUESTION: The D-dimer test goes along with this. What does this show?

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QUESTION: The rapid respiratory rate is a result of the compromised respiratory system. Note the % oxygenation of hemoglobin. But what would be another reason for rapid breathing shown in the table above?

Answer



After the period shown in the table above, the patient continued to have fairly severe respiratory and neurological issues for over a week. But due to the intensive care procedures, he survived and was released from the hospital without apparent issues on day 40, which was 20 days after his various body fluids had been cleared of infectious viral particles. A small amount of viral RNA was still in the sweat, but not in an infectious form.