Outbreaks of adenovirus type 4 (Ad4) acute respiratory disease (ARD) have reemerged among US military personnel during the past decade. A prospective epidemiological investigation of 678 military recruits was conducted at Fort Jackson, South Carolina, in the fall of 1998; 115 (17%) of the recruits were hospitalized for febrile ARD. Adenovirus types 4, 3, and 21 were recovered from the cultures of 70 (72%), 7 (7%), and 2 (2%) of 97 recruits, respectively. In addition, 69 (83%) of the 83 hospitalized and 82 (49%) of the 166 nonhospitalized unit contacts had seroconversion to Ad4, which indicates the very high susceptibility and communicability of Ad4 among military recruits. Young age (<20 years) and male sex increased the risk for anti-Ad4 seroconversion. Recruits from tropical areas had higher preexisting immunity than did recruits from temperate regions. Military recruits are highly susceptible to Ad4 infections. Prompt reinstitution of an adenovirus vaccination program in this high-risk population is urgently needed.

Andes virus (ANDV) and Sin Nombre virus (SNV) are rodent-borne hantaviruses that cause a highly lethal hemorrhagic fever in humans known as hantavirus pulmonary syndrome (HPS). There are no vaccines or specific drugs to prevent or treat HPS, and the pathogenesis is not understood. Syrian hamsters infected with ANDV, but not SNV, develop a highly lethal disease that closely resembles HPS in humans. Here, we performed a temporal pathogenesis study comparing ANDV and SNV infections in hamsters. SNV was nonpathogenic and viremia was not detected despite the fact that all animals were infected. ANDV was uniformly lethal with a mean time to death of 11 days. The first pathology detected was lymphocyte apoptosis starting on day 4. Animals were viremic and viral antigen was first observed in multiple organs by days 6 and 8, respectively. Levels of infectious virus in the blood increased 4 to 5 logs between days 6 and 8. Pulmonary edema was first detected ultrastructurally on day 6. Ultrastructural analysis of lung tissues revealed the presence of large inclusion bodies and substantial numbers of vacuoles within infected endothelial cells. Paraendothelial gaps were not observed, suggesting that fluid leakage was transcellular and directly attributable to infecting virus. Taken together, these data imply that HPS treatment strategies aimed at preventing virus replication and dissemination will have the greatest probability of success if administered before the viremic phase; however, because vascular leakage is associated with infected endothelial cells, a therapeutic strategy targeting viral replication might be effective even at later times (e.g., after disease onset).

The pathogenesis of hepatitis A virus (HAV) infection was studied in owl monkeys following oral administration of the wild-type HM-175 strain of HAV. Stools were collected daily and blood and pharyngeal swabs twice weekly for viral isolation, and animals were necropsied at various intervals after inoculation. Organs were examined for the presence of virus by isolation in cell culture and for viral antigens by immunofluorescence. Monkeys excreted HAV in the stools for 1-4 days after inoculation, presumably due to the residual unabsorbed inoculum. No virus was found in stools for the next 2-3 days. HAV re-appeared on days 4-7 and then persisted through day 39. Viremia occurred on the 10th day and continued until day 35. Virus was isolated occasionally from throat swabs 1 or 2 weeks after it was detected in stools and blood, and there was no evidence that HAV replicated in the pharyngeal tissues. Animals acquired anti-HAV antibody by the 4th week, and alanine aminotransferase (ALT) was elevated 5-5.5 weeks after inoculation. HAV was isolated from liver 5 days after inoculation; however, viral antigens were first detected in Kupffer cells of the liver at 14 days and in hepatocytes at 21 days. HAV antigen was detected in epithelial cells of the intestinal crypts and in the cells of the lamina propria of the small intestine 3 days postinoculation and thereafter until the 5th week, suggesting that these cells might represent an additional site of HAV replication.

Extraintestinally invasive Escherichia coli (EC) that possess both a complete LPS and K1 capsule evade both complement-mediated bacteriolysis and neutrophil-mediated killing. Since C3H/HeJ mice that are hyporesponsive to LPS were uniquely susceptible to lethal infection with EC of this phenotype, we speculated there was an LPS-initiated host defense mechanism against this pathogenic phenotype. The LPS-normoresponsive C3H/HeN as well as the C3H/HeJ mice cleared these EC from the circulation within 4 h of intravenous administration. Whereas electron micrographs of the liver demonstrated these EC undergoing degeneration within the phagolysosomes of of both macrophages and Kupffer cells of C3H/HeN mice, these EC replicated within these cells of the C3H/HeJ mice. Restoration of anti-EC activity of C3H/HeJ mice occurred with activation of Kupffer cells and peritoneal macrophages in vivo with BCG and in vitro with IFN-y, but not with LPS. Pretreatment of C3H/ HeJ mice with a combination of recombinant murine IL-1 and TNF-a also restored the killing of K1 +-EC but did not enhance the killing of a K1--EC mutant. These data are consistent with the hypothesis that (a) there is no intrinsic inability of C3H/HeJ phagocytes to kill EC, but (b) an LPS-initiated, cytokine-mediated host defense mechanism is required for such killing. These studies emphasize the importance of bacterial surface characteristics in the interaction with specific host defenses. (J. Clin. Invest. 1995.

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