Clinical Laboratory Values in Human Ebola Virus Disease Support the Relevance of the Intramuscular Ebola-Kikwit Rhesus Model

To the Editor—We read with interest the recent article in Clinical Infectious Diseases by Lanini et al, which focused on the relationship between human Ebola virus (EBOV) RNA and clinical chemistry values obtained during the West African outbreak in Goderich, Sierra Leone [1]. While many investigators have demonstrated that EBOV viremia is associated with survival [2–6], Lanini et al found that multilevel mixed-effects regression models demonstrated a significant correlation between EBOV viremia and aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine phosphokinase (CPK), lactate dehydrogenase (LDH), international normalized ratio (INR), and adjusted partial thromboplastin time (aPTT). This is important because these findings further support the possibility of using human clinical laboratory values as surrogate markers of EBOV viral load as Janvier et al suggested with regard to AST [7]. Moreover, we recently published that in a linear regression model at 5 days postinfection (dpi) in rhesus macaques exposed to 1000 plaque-forming units (PFU) of EBOV-Kikwit intramuscularly (IM), that platelet counts, prothrombin time (PT), AST, ALT, LDH, and CPK correlated significantly with time to death and with log₁₀ viral RNA [8]. Similarly, we found in a linear regression model that at 7 dpi, LDH and CPK correlated significantly with time to death and with log₁₀ viral RNA. These findings are not surprising given that Warren et al [9] showed that in the 1000 PFU IM EBOV-Kikwit rhesus macaque model, the course of EBOV viral load is mirrored by the clinical chemistry results in the setting of successful Ebola virus disease (EVD) treatment using GS-5734.