Clinical Virology of Lassa Fever in Hospitalized Patients

Abstract

We measured levels of virus in sequential specimens from 137 patients with Lassa fever. The probability of fatal disease increased significantly with the level of viremia measured either on admission or during the course of illness. The odds ratio of death in patients with viremia greater than 10 TCID50/ml was 3.7 (90% confidence interval, 1.9-7.2). The same ratio in patients with viremia greater than 10 TCID50/ml and with levels of aspartate aminotransferase greater than or equal to 150 IU/liter was 21.5 (95% confidence interval, 5.2-99.0). Virus was found in throat cultures from 39% of viremic patients, compared with 14% of nonviremic patients (P less than .002); however, the level of virus was usually less than or equal to TCID50/ml. Fewer than 3% of patients were viruric during acute illness, and virus was isolated from three of three samples of cerebrospinal fluid. On admission, 53% of patients had IgG antibodies, and 67% had IgM antibodies. Recovery was not associated with the presence of either IgG or IgM. Virus was isolated from greater than 100 serum specimens that also contained high titers of IgG. Clinical Lassa fever was shown to be a disseminated systemic, primary viral infection, with an outcome highly associated with viremia but not with development of antibody.

Characterization of the Glycoprotein Stable Signal Peptide in Mediating Pichinde Virus Replication and Virulence

“…Collectively, our data suggest that both the N37A and R55A mutant viruses are attenuated in vivo. It is worth mentioning that, for all mutant viral infections, animals that survived the infection did not contain any trace of infectious virus in the serum while all moribund animals had high viremia as determined by plaque assay, correlating with the previous reports that arenavirus virulence is associated with high levels of viral replication in vivo (3,21,31).…”

“…The most significant arenavirus pathogen is Lassa fever virus (LASV), which causes infections that are endemic to many countries in West Africa, with an estimated 500,000 cases resulting in ϳ5,000 deaths annually (3). Except for Junin virus (JUNV), which has a vaccine, Candid#1, used only in Argentina, no licensed vaccine for human use is currently available for any other arenaviruses.…”

“…A low-passaged strain of PICV (i.e., P2) causes a brief febrile reaction in guinea pigs, while a high-passaged strain (i.e., P18) causes a severe Lassa fever-like disease in guinea pigs with high mortality (3,(13)(14)(15)(16)(17). We have developed infectious clones for both the nonvirulent P2 strain and the virulent P18 strain of PICV (18) and characterized the virulence determinants at the molecular level (19)(20)(21).…”

Analytical Validation of the ReEBOV Antigen Rapid Test for Point-of-Care Diagnosis of Ebola Virus Infection

“…Following the initial animal-to-human transmission event, EBOV has demonstrated considerable capability for human-to-human transmission [3,4]. EVD clinical manifestations can easily be confused with those of other endemic febrile illnesses, including malaria, typhoid fever, and Lassa fever, where misdiagnosis can lead to fatal consequences [5][6][7][8]. Advanced disease can result in spontaneous abortion, delirium, coma, or hemorrhage [8].…”

Lassa Virus Infection of Human Dendritic Cells and Macrophages Is Productive but Fails to Activate Cells

“…Humoral responses cannot control viral replication and the appearance of specific IgG in patients and infected monkeys is not correlated with recovery (11,12). The induction of cellular responses specific for viral glycoproteins protects nonhuman primates from a lethal challenge (12), and memory CD4 ϩ T cell responses against NP have been demonstrated in seropositive endemic subjects (13).…”