Filoviruses and Arenaviruses

Maintenance in Nature and Transmission to Humans

Filoviruses and arenaviruses are zoonotic, with the endemic area for each virus restricted by the distribution of its animal reservoir. ^{, ,} Zoonotic transmission of filoviruses and arenaviruses to humans usually occurs through inadvertent exposure to animal excreta or saliva or, in some cases, blood and other body fluids when infected animals are hunted and butchered. ^, Because the filoviruses and arenaviruses are rapidly inactivated by heating, infection likely occurs through exposure during preparation rather than by consumption of cooked meat.

Bats are thought to be the filovirus reservoir. Marburg virus was isolated from Rousettus aegyptiacus fruit bats. Ebola virus (species Zaire ebolavirus ) was detected by reverse transcriptase polymerase chain reaction (RT-PCR) in three species of bats ( Hypsignathus monstrosus , Epomops franqueti , and Myonycteris torquata ). Miners, spelunkers, forestry workers, and others with exposure to environments where bats typically roost are at risk of filovirus infection. Nonhuman primates, especially gorillas and chimpanzees, and other wild animals can serve as intermediate hosts for filoviruses. These animals are presumably infected by exposure to bats and develop severe and usually fatal disease similar to that in humans.

Pathogenic arenaviruses are maintained in rodents, with strict pairing between the specific virus and animal reservoir ( Table 230.1 ). ^{, ,} The rodents that transmit Lassa virus, Machupo virus, and LCMV commonly invade domestic environments. LCMV has a worldwide distribution because of the pervasiveness of its rodent reservoirs. The virus has been found in both wild and pet rodents, including mice and pet hamsters. Transmission to humans occurs as a result of exposure to the rodent reservoir’s bodily fluids, as occurs during a rodent bite or aerosolization of urine. The reservoirs for Junín and Guanarito viruses typically inhabit agricultural fields, wood lots, or other rural habitats.

Most human Lassa fever virus infections are acquired directly from rodents as indicated by greater genetic diversity in case clusters than would be expected within chains of human transmission. ^, Peak incidence occurs during the dry season of November through April in endemic areas. Geographic distribution is necessarily limited to the range of the respective rodent reservoir and habitat. For Lassa fever virus, the reservoir species of Mastomys and Hylomyscus genera thrive in peridomestic areas, distributing risk of infection across sex, age, and occupation. ^, Studies have reported a prevalence of 5% to 20% in Mastomys natalensis , highlighting the pervasiveness of infection risk.

In contrast to Lassa fever virus, there are intermittent outbreaks and fewer reported cases of New World arenaviruses. In 2019, an outbreak of 5 cases including two nosocomial infections (3 fatalities) of Chapare hemorrhagic fever occurred in Bolivia, and a fatal Sabia-like case occurred in Sao Paulo, Brazil. ^, As with Lassa fever virus, periods of increased incidence correspond with seasonal agricultural activity, since fields are a preferred habitat for many New World arenavirus rodent reservoirs.

Human-to-Human Transmission

Although attack rates usually are low for filoviruses and arenaviruses (15%–20%, even for Ebola Zaire virus, which probably is the most transmissible), secondary human-to-human transmission does occur ( Table 230.1 ), as seen most dramatically in the 2013–2016 Ebola Zaire virus outbreak in West Africa. Large outbreaks typically are fueled by nosocomial transmission in resource-poor regions, where basic infection control practices cannot be maintained. Infectivity parallels the clinical state, and people are most infectious late in the course of severe disease. There is no evidence of transmission during the incubation period.

Transmission occurs through direct contact with blood or body fluids and probably occurs through oral or mucous membrane exposure, most often in the context of providing care to a sick family member (i.e., community exposure) or patient (i.e., nosocomial transmission), or by participation in burial rituals that involve washing and touching corpses. Infection through fomites cannot be excluded but is probably not common unless the object is obviously contaminated with blood or body fluids. ^, Human to human transmission of LCMV has been documented only in the context of organ transplantation.

Sexual transmission from virus persistence in the semen has been identified more than 3 years after recovery from Ebola virus infection (species Zaire ebolavirus). Although not specifically documented, virus persistence and the risk of sexual transmission is presumed for the other pathogenic species of Ebolavirus . Sexual transmission and virus persistence in semen was detected 7 weeks after recovery from Marburg virus infection. Viral persistence in semen has also been noted up to 103 days after recovery in Lassa survivors and up to 176 days after recovery in Chapare survivors. ^,

Detection of virus by RT-PCR in breast milk has been documented for Ebola virus (species Zaire ebolavirus ) and Marburg virus and breastfeeding may be a factor in virus transmission. Although not specifically documented, virus persistence and the risk of disease transmission through infected breast milk is presumed for the other pathogenic species of Ebolavirus . Congenital transmission have been documented for Ebola virus (species Zaire ebolavirus ) and although not specifically documented, is presumed for the other pathogenic species of Ebolavirus and Marburgvirus . Congenital transmission appears uncommon with Lassa fever virus infection, but asymptomatic or mild maternal cases makes it difficult to assess. Given the presence of Lassa fever virus in breast tissue and bodily fluids, nursing may carry a risk to an infant.

Although infectious aerosols have been artificially produced in the laboratory, which is a concern because of the potential for their use in biowarfare, epidemiologic and limited laboratory-based data do not suggest aerosol transmission between humans in natural settings. ^{, ,}

Filoviruses

The clinical presentation and course of filovirus infections share significant overlap. Filovirus infections are seen in both sexes and all age groups, with a spectrum from mild infection to rapidly fatal disease. ^, Although serosurveys have suggested asymptomatic infection is possible, it is likely rare and not as common as seen in arenavirus infections. ^, It is usually not possible to distinguish the specific infecting virus by clinical manifestations.

After an incubation period of 2–21 days (usually 4–17 days), patients typically have nonspecific signs and symptoms, including fever, general malaise, anorexia, headache, chest or retrosternal pain, sore throat, myalgia, arthralgia, lumbosacral pain, and dizziness. Approximately 4 days after symptom onset, gastrointestinal signs and symptoms ensue rapidly, including nausea, vomiting, epigastric and abdominal pain, abdominal tenderness, and diarrhea, which in EVD can be voluminous. ^{, , ,} Misdiagnosis as acute appendicitis or other abdominal emergencies can occur. A dry cough with a few scattered rales is common, but prominent pulmonary symptoms are rare early in the course of the disease. Jaundice is not typical and suggests a different diagnosis. Morbilliform, maculopapular, petechial, and ecchymotic rashes can occur.

A subset of patients with filovirus infection will progress to vascular instability marked by conjunctival injection (not accompanied by itching, discharge, or rhinitis), hemorrhage, hypotension, and multi-system organ failure. Hemorrhage can manifest as hematemesis, melena, hematochezia, metrorrhagia, petechiae, purpura, or epistaxis. Bleeding from the gums and venipuncture sites may arise, but hemoptysis and hematuria are uncommon ( Fig. 230.1 ).

In fatal cases, death occurs about 8–10 days after onset of disease for the filoviruses and 10–14 days for arenaviruses. Shock, bleeding, neurologic manifestations, high levels of viremia, elevated levels of aspartate aminotransferase (>150 IU/L), and pregnancy, especially during the third trimester, are indicators of a poor prognosis. The mortality rate is especially high for children aged <5 years. ^{, , ,}

Common clinical laboratory findings are summarized in Table 230.2 . Radiographic and electrocardiographic findings usually are nonspecific and correlate with the physical examination findings. ^,

Pregnant women often come to medical attention because of spontaneous abortion and vaginal bleeding. However, a few Ebola virus–infected pregnant women have had mild or atypical clinical manifestations, posing a diagnostic dilemma. Despite slightly improved survival of pregnant women during the 2013–2016 outbreak in West Africa, pregnancies result in miscarriage, stillbirth, or early neonatal death. There is one report of a neonate born to an infected mother, who received various experimental therapies, surviving beyond the neonatal period. ^, Rarely, women who were infected during pregnancy have survived acute EVD without aborting, only to experience a stillbirth of a macerated fetus in the subsequent weeks. The stillborn fetuses were confirmed to be positive for the virus by RT-PCR testing, despite no evidence of persistent Ebola virus in the mothers’ blood. This may result from the relative immune privilege of the intrauterine compartment during pregnancy and the immaturity of the fetal immune system.