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Volume 21, Number 1—January 2015

Health Care Response to CCHF in US Soldier and Nosocomial Transmission to Health Care Providers, Germany, 2009

Nicholas G. CongerComments to Author , Kristopher M. Paolino, Erik C. Osborn, Janice M. Rusnak, Stephan Günther, Jane Pool, Pierre E. Rollin, Patrick F. Allan, Jonas Schmidt-Chanasit, Toni Rieger, and Mark G. Kortepeter1
Author affiliations: Landstuhl Regional Medical Center, Landstuhl, Germany (N.G. Conger, E.C. Osborn, J. Pool, P.F. Allan); Walter Reed Army Institute of Research, Silver Spring, Maryland, USA (K.M. Paolino); Force Health Protection, Fort Detrick, Maryland, USA (J.M. Rusnak); Bernard Nocht Institute, Hamburg, Germany (S. Günther, J. Schmidt-Chanasit, T. Rieger); Centers for Disease Control and Prevention, Atlanta, Georgia, USA (P. Rollin); Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA (M.G. Kortepeter)

Main Article

Table 1

Results of laboratory testing and regimen for ribavirin treatment for a US soldier with CCHF, Germany, 2009*

Treatment/test or procedure Day after symptom onset, date
Reference range
Day 6, Sep 11 Day 7, Sep 12 Day 8, Sep 13 Day 9, Sep 14 Day 10, Sep 15 Day 11, Sep 16
Ribavirin treatment†
RT-PCR, RNA copies/mL‡ 1.2 × 109 ND 6 × 109 ND 3 × 108 ND NA
Dialysis ND ND Renal Renal/hep Renal/hep Renal NA
CCHF culture§ + ND ND ND ND ND
IgM/IgG¶ −/− ND −/− ND +/+ ND
Hemoglobin, g/dL 12.8 7.7 9.1 11.9 9.9 8.5 13.2–17.1
Hematocrit, % 35.3 21.6 25.4 33.5 27.7 23.7 38–50
Leukocyte count, × 103/μL 9.6 8.8 4.9 4.0 3.4 3.5 3.5–10.5
Platelets, × 103/μL 14,000 68,000 62,000 93,000 126,000 77,000 151–356
Creatinine, mg/dL 7.8 8.7 5.1 2.7 1.4 0.9 0.8–1.5
BUN, mg/dL 67 72 32 8 2 <2 8–26
Sodium, mmol/L 140 146 143 142 141 147 137–145
Potassium, mmol/L 4.7 5.2 4.0 5.0 4.3 3.4 3.6–5.1
Bicarbonate, mmol/L 20 12 19 18 28 33 22–31
Chloride, mmol/L 110 102 98 103 100 101 101–111
Lactate, mmol/L 3.0 14.9 17.8 8.7 7.7 7.4 0.7–2.1
Glucose, mg/dL 92 187 93 68 82 89 74–106
AST, U/L 1,472 3,957 11,295 9,628 9,061 5,967 15–41
ALT, U/L 411 1,838 2,854 2,151 1,805 1,122 17–63
LDH, IU/L 756 ND ND ND ND ND 98–192
Alkaline phos, UL 186 123 163 202 254 354 38–126
Total, mg/dL 1.8 5.8 6.7 8.1 9.2 10.4 0.2–1.3
Direct, mg/dL 1.1 ND 3.3 3.2 3.0 3.0 0.1–0.3
aPTT, s 106.9 89.8 56.6 59.3 67.4 52.7 28.2–40.3
Prothrombin time, s 21.8 22.4 22.3 14.9 19.7 24 11.9–15.1
Fibrinogen, mg/dL 143 190 238 156 153 111 168–407
D-dimer, µg/dL 20 ND ND ND ND ND <5
Albumin, g/dL 2.8 2.8 3.7 4.2 4.7 4.8 3.5–5.0
CPK, U/L 1,437 1,528 1,889 3,008 4,728 4,973 55–170
Myoglobin, ng/mL 1,226.5 ND ND ND ND ND 17.4–105.7
Malaria smear −** ** ** ** ** ** NA
Bacterial cultures# −** ** ** ** ** ** NA
X-ray/CT, chest ND Moderate to severe pulmonary edema and atelectesis ND ND ND ND NA
CT, abdomen ND Ascites, gallbladder edema ND ND ND ND NA
10, pg/mL †† 515 ND 1,498 ND 904 ND <7
6, pg/mL †† 1,530 ND >3,023 ND 2,439 ND <15
IFN-γ, pg/mL †† 59 ND 390 ND 125 ND <15
TNF-α, pg/mL †† 77 ND 56 ND 100 ND <15
Growth factors
PLGF, pg/mL †† 203 ND 64 ND 81 ND <25
sVEGF-R1, pg/mL †† 2,930 ND 13,903 ND 13,308 ND <180

*aPTT, activated partial thromboplastin time; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; CCHF, Crimean–Congo hemorrhagic fever; CPK, creatine phosphokinase; CT, computerized tomography; hep, hepatic; IFN-γ, interferon γ; IV, intravenously; LDH, lactate dehydrogenase; NA, not applicable; ND, not determined; phos, phosphatase; PLGF, placental growth factor; RT-PCR, reverse transcription PCR; sVEGF-R1, soluble vascular endothelial growth factor receptor 1; TNF-α, tumor necrosis factor α; −, negative; +, positive.
†On day 6, an initial 4-g loading dose (LD) of oral ribavirin was administered via nasogastric tube, followed by 1,200 mg 6 h later. On day 7, a partial LD of 22 mg/kg was administered IV (because of 60% bioavailability of oral ribavirin and poor absorption with gastrointestinal bleeding) followed by 16-mg/kg doses every 6 h (per dose-reduction protocol). Beginning day 9, 14 mg/kg was administered every 6 h, with an extension of the dosing interval to every 8 h on day 10 because of severe renal failure (only a minimal amount of drug is removed through dialysis) (3).
‡Real-time RT-PCR for virus quantification and Nairovirus spp.–specific gel-based RT-PCR coupled with PCR product sequencing to confirm the diagnosis (6,7).
§CCHF culture of blood and urine (virus was isolated on Vero cells and sequenced) (8).
¶CCHF-specific IgM/IgG by indirect immunofluorescence assay using CCHF virus–infected cells; assay performed at Bernard Nocht Institute, Hamburg, Germany.
#Culture of blood, urine, and sputum samples.
**Malaria smear and culture results were not specifically obtained on day 6; multiple cultures were performed.
††Testing for cytokines and vascular endothelial growth factors and their soluble receptors of blood were performed in the Biosafety Level 4 facility of Bernard Nocht Institute by using Quantikine Immunoassays (R&D Systems Europe, Abingdon, UK), according to the manufacturer’s instructions.

Main Article

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Main Article

1Preliminary results from this study were presented at the Annual Meeting of the Armed Forces Infectious Disease Society; May 23, 2010, San Antonio, Texas, USA; NATO Biomedical Advisory; May 27, 2010, Munich, Germany; and Asian Pacific Military Medicine Conference, May 3, 2011, Sydney, New South Wales, Australia.

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