Six naturally occurring types of HFs in humans are currently recognized in the Americas: Argentine, Bolivian, Venezuelan, Brazilian, Whitewater Arroyo virus, and Chapare virus HFs. These are caused by the Junin, Machupo, Guanarito, Sabia, Whitewater Arroyo, and Chapare viruses, respectively, and belong to the Tacaribe (New World) serocomplex of the Arenaviridae family. This complex is composed of three clades: clade A consists of the pathogenic Whitewater Arroyo and the nonpathogenic Tamiami and Bear Canyon viruses, all from North America, and Pichinde, Parana, Pirital, Flexal, and Allapahuayo South American viruses; clade B contains the pathogenic Junin, Machupo, Guanarito, Sabia, and Chapare viruses and the nonpathogenic Tacaribe, Amapari, and Cupixi viruses; and clade C contains the nonpathogenic Oliveros, Latino, and Pampa viruses. However, a recent report places the three North American viruses in a distinct group. On the average, a new member of the serocomplex is found every three years. They are transmitted by sigmodontine rodents, and with the exception of the Whitewater Arroyo virus, pathogenic members are restricted to South America. The Old World arenavirus found in North America is the lymphocytic choriomeningitis virus.

The American HF viruses pose unique challenges: infection with these viruses leads to a high mortality rate, vaccines against the majority of these agents are lacking, and infection may occur via inhalation. These factors, together with the low numbers of organisms required to infect a human, make these viruses good candidates for weaponization and therefore agents of special concern to the world community. Fortunately, several effective treatment options are available for use for individuals afflicted by American hemorrhagic fevers, which is not the case for some of the other hemorrhagic fevers, including one caused by infection by the Old World arenavirus Lassa fever (discussed in Chapter Fourteen).

Argentine hemorrhagic fever was first described as a clinical disease in 1955 in an epidemic in Bragado, Argentina, in Buenos Aires Province. The endemic area for this disease is continuing to spread over this province and parts of Sante Fé and Cérdoba provinces. The Junin virus, the causative agent, was subsequently isolated in 1958 in the city of Junín. Between 1958 and 1987, about 21,000 cases of Argentine HF were reported.

Scattered cases of “black typhus” began in the Bolivian Amazon River basin in 1959. The outbreak of this disease, now known as Bolivian hemorrhagic fever, resulted in 470 cases and 142 deaths (30% fatality rate) between 1959 and 1962. In the 1960s, there were large epidemics with many deaths. In one town with 3,000 residents, 600 cases occurred, with 113 deaths recorded in two years (20% incidence, 19% fatality rate). These epidemics were finally stopped by the use of mousetraps and oil-grain baits containing zinc phosphide to eliminate the rodent vector. The causative arenavirus, the Machupo virus, was first isolated in 1963. There were no cases between 1973 and 1992. A familial cluster of patients was reported in 1994.

In September 1989, an outbreak of severe febrile disease was noted in Portuguesa, Venezuela. This outbreak was confined mainly to rural inhabitants in the southern portions of the state. A total of 105 confirmed or probable cases of Venezuelan hemorrhagic fever occurred from September 1989 to May 1995. Many of the cases originated near Guanarito, in the Portuguesa state.

The first reported case of Brazilian hemorrhagic fever occurred in a 25-year-old female agricultural engineer in Sã Paulo state in 1990 and was fatal even after treatment with defoxitin and amikacin. She had worked mainly in an office. A lab worker later became infected, probably via an aerosol, was treated with intravenous fluids, and recovered. A second infected lab worker was put on intravenous ribavirin, an antiviral agent, and the fever disappeared within two days.

Flexal virus has not been reported to cause natural infection in humans yet but has resulted in moderately severe infections in two laboratory workers. It must therefore be regarded as a potential danger.

In 1999 and 2000, three cases of hemorrhagic fever caused by Whitewater Arroyo virus occurred in California. All three were fatal. The virus itself was first isolated from whitethroat woodrats in New Mexico in 1996.

The most recently discovered pathogenic member of the Tacaribe group is the Chapare virus. This clade B virus caused a cluster of infections, including one fatal case of hemorrhagic fever in a remote region of the Andes mountains of rural Bolivia in 2008. Little information about this virus is currently available.

The American hemorrhagic fevers closely resemble dengue, yellow fever, idiopathic thrombocytopenic purpura, and other illness whose symptoms include prolonged fever with leukopenia and hemorrhagic signs. The prodrome (early warning signs) includes fever, sore throat, and muscle and retro-ocular pain. The infectious dose for these viruses is one to ten organisms, followed by an incubation period of 7 to 14 days. Symptoms occurring during the early stages of infection include headache, weakness, flushing of the face and thorax, petechial and erythematous rashes, anorexia, nausea and vomiting, and lymphadenopathy.

Later during the course of disease, various vascular abnormalities occur, and many patients are hospitalized. Thrombocytopenia leads to the development of small focal hemorrhages in many organs, particularly the liver (hepatocellular necrosis). The diarrhea is bloody. The number of eosinophils increases, but the total number of white blood cells decreases with both neutropenia and lymphoid depletion and necrosis in the spleen and lymph nodes. Increased vascular permeability may result in hemoconcentration. Hemorrhagic manifestations include nosebleed, bleeding gums, bloody vomit, and massive gastrointestinal hemorrhages. The spleen may enlarge and become congested. Low blood pressure may lead to shock. There is extensive infection of macrophages and, in Argentine HF, dendritic cells as well, but not lymphocytes. Lymphocyte loss in Argentine HF may be due at least in part to apoptosis. There is minimal involvement of the endothelium, with no specific vascular lesions found in infected monkeys. Substantial changes in coagulation and fibrinolysis markers may be found, including complexes of thrombin and antithrombin, prothrombin fragments, protein C, D-dimers, tissue plasminogen activator, and plasminogen activator inhibitor-1. Levels of the acute-phase proteins fibrinogen and von Willebrand factor are also increased. These changes may be caused by the presence of proinflammatory cytokines.