Current Diagnosis & Treatment in Infectious Diseases

Section IV - Viral Infections

44. Miscellaneous Systemic Viral Syndromes

Lawrence W. Drew MD, PhD

This chapter includes a variety of viral infections that produce severe systemic syndromes (Table 44-1). In some cases, these infections are transmitted by arthropod vectors; in others, they are acquired by direct contact with the reservoir animal or its excreta. The illnesses may be hemorrhagic fever (eg, dengue, Marburg, Ebola, or Lassa fevers), generalized fever (yellow fever or Colorado tick fever), or pneumonia (caused by hantavirus infection). Only two of these are endemic in the United States, hantavirus infection and Colorado tick fever. All of these viruses are RNA viruses, and vaccine has been developed for one (yellow fever).

DENGUE & YELLOW FEVER

General Considerations

Dengue and yellow fever are both caused by flaviviruses, and each is spread by an arthropod vector. The etiologic agents of dengue are the dengue virus types 1–4, whereas yellow fever is caused by the yellow fever virus. Flaviviruses produce a wide range of diseases including hemorrhagic fevers, arthritis, encephalitis, and hepatitis. Hepatitis C is caused by a flavivirus and is discussed in Chapter 40. Until recently the flaviviruses were included in the Togaviridaefamily, but differences in size, morphology, gene sequence, and replication strategy have made it necessary to classify them as an independent virus family.

  1. Epidemiology

The flaviviruses are also classified as arboviruses (see Chapter 43) because they are usually spread by arthropod vectors and as zoonotic viruses because they are spread by animals. These viruses have a very broad host range, including vertebrates (eg, mammals, birds, amphibians, and reptiles) and invertebrates (eg, mosquitoes and ticks).

A cycle of infection occurs in which the virus is transmitted by the arthropod vector and amplified in a susceptible host to allow reinfection of other arthropods. Humans are usually dead-end hosts that cannot spread the virus back to the vector because a persistent viremia is not maintained.

These viruses are maintained by Aedes spp. mosquitoes in a sylvatic or jungle cycle, in which monkeys are the natural host, and also in an urban cycle, in which humans are the host. A aegypti is a vector for each of these viruses and is a household mosquito. It breeds in pools of water, open sewers, and other accumulations of water in cities.

Dengue occurs throughout the world, with long-known endemic areas in tropical Asia, Polynesia, Micronesia, and East and West Africa. In recent years there has been an upsurge of dengue in South and Central America, the Caribbean, and India, and the spread is predominantly human-mosquito-human, with persistent viremia in the human allowing infection of mosquitoes. Yellow fever is also found in the Caribbean and the tropics, including Africa but not Asia, and the spread is monkey to mosquito (A aegypti) to monkey or to human. In the past decade there has been a major increase in cases especially in Africa. Dengue is the most prevalent flavivirus and causes ≤ 100 million infections/year. In the past, dengue occurred in outbreaks within the United States, and the presence of A aegypti and A albopictus, another potential vector, in the coastal southern United States means that future outbreaks could occur.

  1. Microbiology

The flaviviruses are spherical (40–60 nm) enveloped, positive, single-stranded ribonucleic acid (RNA) viruses. They attach to specific receptors expressed on many different cell types from many different species. Flaviviruses can also attach to the Fc receptors on macrophages, monocytes, and other cells when they are coated with antibody. The antibody actually enhances the infectivity of these viruses by providing new receptors for the virus and by promoting its uptake into these target cells.

The virus enters the cell by receptor-mediated endocytosis. The envelope fuses with the membrane of the endosome on acidification of the vesicle to deliver the capsid and genome into the cytoplasm.

Once released into the cytoplasm, the flavivirus genomes are translated via complementary RNA into several proteins. Assembly and budding of flaviviruses occur predominantly in the cytoplasm by using intracellular membranes or vesicles, rather than at the cell surface. Virus release occurs during lysis of the cell.

Table 44-1. Important viral fevers.

Family

Agent

Reservoir/Vector

Disease

Outbreak Locations

Route of Transmission

Mortality (%)

Arenaviridae

 

Machupo

Vesper mouse (R)

Bolivian hemorrhagic fever

Bolivia

Inhalation of dried rodent excreta

10–20

 

Lassa

Mastomys rodents (R)

Lassa fever

West Africa including hospital workers

Inhalation of dried rodent excreta plus person-to-person (body fluids)

15–25

Flaviviridae

 

Yellow fever virus

Humans, simians (R) Aedes aegypti (V)

Yellow fever

Equatorial Africa, South America

Mosquito bite

10

 

Dengue (1–4)

Human (R), &monkeys, Aedes, ticks (V)

Dengue fever (DF) Dengue hemorrhagic fever (DHF)

Tropical worldwide

Arthropod bite

DF = 0; DHF = 15

Bunyaviridae

 

Phleboviruses:

 

Rift Valley

Cattle, sheep (R) Aedes, others (V)

Rift Valley fever

South Africa—sheep Egypt-Aswan Dam Mauritania-Senegal R. Dam

Mosquito bite

1

 

Hantaviruses:

 

Sin Nombre

Deer mouse (R)

Hantavirus pulmonary syndrome

Southwestern United States

Inhalation of dried rodent excreta

10–50

 

Nairoviruses:

 

Congo

Hares, hedgehogs, ticks (V)

Congo-Crimean hemorrhagic fever

Western Russia, Balkans, East Africa

Tick bites plus person-to-person (blood)

20–50

Filoviridae

 

Marburg

Unknown

Marburg virus disease

Germany, Yugoslavia—lab workers: South Africa; Kenya

Person-to-person (body fluids)

20–25

 

Ebola

Unknown

Ebola hemorrhagic fever

Sudan Zaire

Person-to-person (body fluids)

70–90

Reoviridae

 

Coltvirus

Mammals (squirrels, chipmunks, rabbits, deer); tick (D andersoni)

Colorado tick fever

Western United States and Canada

Tick bite

<1



  1. Pathogenesis

The flavivirus can cause lytic or persistent infections of both vertebrate and invertebrate hosts. Infections of invertebrates are usually persistent, with continued virus production and no damage to the insect.

Female mosquitoes acquire the flaviviruses on taking a blood meal from a viremic, vertebrate host. The virus infects the epithelial cells of the mid-gut of the mosquito, spreads through the basal lamina of the mid-gut to the circulation, and then infects the salivary glands. The virus sets up a persistent infection and replicates to high titers in these cells. The salivary glands can then release virus into the saliva.

After biting a host, the female mosquito regurgitates virus-containing saliva into the victim's bloodstream. The virus circulates transiently in the plasma, and primary replication occurs in lymph nodes.

The initial viremia, after replication of the virus in these tissues, produces systemic symptoms such as fever, chills, headaches, backaches, and flulike symptoms within 3–7 days of infection. Some of these symptoms can be attributed to the interferon produced after infection of these target cells. Most yellow fever infections do not progress beyond this point, but secondary multiplication of virus occurs in liver, spleen, kidneys, heart, and bone marrow with severe toxicity.

  1. Immune Response.Both humoral and cellular immunities are elicited and are important to the control of primary infection and prevention of future infections with the flaviviruses. Unlike viruses that initially replicate in the lung, intestine, or viscera, the primary infection by these viruses is in lymph nodes. This presents the virus immediately to macrophages, the reticuloendothelial system, and the immune response.

Replication of the flaviviruses in the macrophage and endothelial cells produces a double-stranded RNA replicative intermediate that is a good inducer of interferon. The interferon produced soon after infection is released into the bloodstream to limit further replication of virus and stimulate the immune response. The interferon also causes the rapid onset of flulike symptoms characteristic of mild systemic disease.

Circulating immunoglobulin M (IgM) is produced within 6 days of infection, followed by IgG. The antibody blocks the viremic spread of the virus and subsequent infection of other tissues. Immunity to one flavivirus can protect against other flaviviruses by recognition of the common antigens expressed on all members of the viral family. One example of this may be occurring in the Far East, where Japanese encephalitis but not yellow fever virus is endemic despite the presence of the A aegypti mosquito vector for yellow fever.

Cell-mediated immunity is also important in control of the primary infection. Natural killer cells, T-cells, and macrophages are activated by interferon and can respond to the cell surface antigens displayed on the infected cells.

Immunity to these viruses is a double-edged sword. Inflammation resulting from the cell-mediated immune response can destroy tissue. Prior immunity can promote hypersensitivity reactions such as delayed-type hypersensitivity, formation of immune complexes with virions and viral antigens, and activation of complement. A non-neutralizing antibody can also enhance uptake of the flaviviruses into macrophages and other cells that express Fc receptors. Such an antibody can be generated to a related strain of virus in which the neutralizing epitope is not expressed or different. The consequences of such partial immunity can be devastating. For example, prior infection by one strain of dengue virus will predispose an individual to dengue hemorrhagic fever (DHF) when infected by another strain of dengue. The weakening and rupture of the vasculature are believed to result from activation of complement and other hypersensitivity reactions. In 1981 an epidemic of dengue-2 virus in Cuba infected a population previously exposed to dengue-1 (between 1977 and 1980). More than 100,000 cases of DHF-dengue shock syndrome (DHF/DSS) resulted, with 168 deaths.

Clinical Findings

  1. Signs and Symptoms

Dengue: After an incubation period of 5–6 days, dengue infection may be asymptomatic or associated with a nonspecific illness or with classical dengue. The latter consists of fever, erythematous rash, and severe myalgias involving the back, head, muscles, and joints. The severity of the myalgia is reflected in the alternative name “breakbone fever.” After 1–2 days of fever and rash, the patient's high temperature returns to normal, only to recur 3–4 days later. The recurrence of fever is followed by a second rash that involves face, trunk and limbs but not palms or soles. The fever abates as the second rash develops.

Between the two febrile periods the patient remains symptomatic with gastrointestinal or respiratory symptoms or both. Generalized lymphadenopathy is often present. Resolution occurs in the second week, and fatalities are very rare. On rechallenge with a related strain, dengue can cause severe hemorrhagic disease and shock (DHF/DSS), which occur in tens to hundreds of thousands of cases per year. The hemorrhagic-shock symptoms are attributed to rupture of the vasculature, internal bleeding, and loss of plasma. In addition there is high fever, nausea or vomiting, ecchymosis, and edema of the hands and face.

Yellow fever: The incubation period of yellow fever is 3–6 days. Most infections with yellow fever virus are subclinical or anicteric. Icteric yellow fever infections are characterized by severe systemic disease, with failure of the liver, kidney, and heart and hemorrhage of blood vessels. Liver involvement leads to the jaundice from which the disease obtains its name, but massive gastrointestinal hemorrhages (so-called “black vomit”) may also occur.

Diagnosis

The principal means of diagnosis is antibody assay, and a variety of serologic methods can be used to diagnose infections. A fourfold increase in titer or seroconversion between acute and convalescent sera is used to indicate a recent infection. The serologic cross-reactivity between viruses in a group or complex limits identification of the actual viral species in many cases. IgM and complement fixing (CF) antibodies are short-lived (1–2 months) and can be useful in documenting acute infection. Demonstrations of viral antigen or viral RNA (by polymerase chain reaction [PCR] assay) in blood or tissue can also prove the diagnosis.

Laboratory Findings

Leukopenia is typical; thrombocytopenia is especially prominent in DHF and yellow fever. Abnormal clotting parameters occur in both, as do increases in liver enzymes. Jaundice occurs in yellow fever, not dengue. Rising creatinine may occur in both diseases.

Flaviviruses can be grown in both vertebrate and mosquito cell lines but are difficult and dangerous to isolate. In addition to cytopathology, the viruses grown in culture can be detected by immunofluorescence or by hemadsorption of avian erythrocytes. After isolation the viruses can be distinguished by RNA analysis or immunoassays.

Treatment

No treatment exists for flavivirus diseases other than supportive care.

Prognosis

The fatality rate from DHF is up to 15% as a result of multiple organ failures. The mortality rate from yellow fever is approximately 10% and also results from multiple organ failures (liver, kidney, and heart).

Prevention & Control

The easiest means to prevent the spread of flaviviruses is elimination of its vector and breeding grounds. After the discovery by Walter Reed and colleagues that yellow fever was spread by Aedes aegypti, the number of cases was reduced by controlling the mosquito population.

Vaccination provides effective protection. A live vaccine (17D) is available against yellow fever virus, for individuals working with the virus or at risk for contact. International travelers to yellow fever-endemic zones should be immunized.

The yellow fever vaccine is attenuated from the 17D strain isolated from a patient in 1927 and passaged extensively in monkeys, mosquitoes, embryonic tissue culture, and embryonated eggs. The vaccine elicits lifelong immunity to yellow fever and possibly other cross-reacting flaviviruses. Vaccines against dengue virus are also being developed.

MARBURG & EBOLA VIRUS

General Considerations

Two unique RNA viruses, the Marburg and Ebola viruses, are members of a new family known as filoviruses. These agents can cause severe or fatal hemorrhagic fevers and are endemic in Africa. Laboratory workers have been exposed to the Marburg agent while working with tissue cultures from African green monkeys. Travelers in or residents of central Africa (eg, Zaire or the Sudan) may be infected by the Ebola virus.

  1. Epidemiology

Marburg virus infection was first detected among laboratory workers in Marburg, Germany, who had been exposed to tissues from apparently healthy African green monkeys. However, it is not clear that these monkeys were, or are, the reservoir for this virus because inoculation of Marburg virus into these monkeys produces death rather than a carrier state. Rare cases of Marburg virus infection have been reported in Zimbabwe and Kenya.

Ebola virus has caused disease only in Zaire and the Sudan. In rural areas of central Africa, ≤ 18% of the population have antibody to this virus, suggesting that subclinical infections do occur. The source of the virus and means of transmission are unknown but are possibly simian viruses. Rarely, secondary cases of filovirus infections have occurred in healthcare workers, usually as a result of accidental needle-stick exposure.

  1. Microbiology

Filoviruses are single-stranded RNA viruses with a filamentous or threadlike appearance. The filamentous forms have a diameter of 80 nm but may vary in length from 1,000 to ~14,000 nm. Their symmetry is helical, and they are enveloped. Virus is replicated in the cytoplasm and is released by budding from the cell membrane.

Clinical Findings

  1. Signs and Symptoms.Illness usually begins with flulike symptoms such as headache and myalgia. Within a few days, nausea, vomiting, and diarrhea occur; a rash may often develop. Subsequently, there is hemorrhage from multiple sites and death.
  2. Laboratory Findings.Lymphopenia followed by neutrophilia and severe thrombocytopenia.

Diagnosis

  1. Direct Examination.Direct fluorescent-antibody (FA) assay can detect viral antigens in tissues; virions can be seen by electron microscopy in serum or liver tissue.
  2. Culture

Isolation of the virus is the procedure of choice to diagnose filovirus infections. Marburg virus may grow rapidly in tissue cultures (Vero cells), although Ebola virus recovery may require animal (eg, guinea pig) inoculation. All specimens for filovirus diagnosis must be handled with extreme care to prevent accidental infection.

  1. Serology

IgG and IgM antibodies to filovirus antigens can be detected by immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA), or radioimmunoassay (RIA). Seroconversion or a fourfold rise of IgG antibody levels is diagnostic of active infection, as is the detection of specific IgM antibody.

Treatment

No treatment is known.

Prognosis

The mortality rate in patients with symptomatic Marburg or Ebola virus infection is ≤ 80%.

Prevention & Control

Since the source of filoviruses is unknown, no measures are available for preventing primary infection. Secondary cases in healthcare workers can be prevented by avoiding exposure to contaminated needles, blood, and so on.

HANTAVIRUSES

Essentials of Diagnosis

  • Acute severe respiratory infection in a young adult.
  • Exposure to deer mice, eg, in a remote cabin.
  • Occurrence of disease in far western United States, especially Four Corners states.
  • Diagnosis by serology.
  • Can detect viral RNA by PCR of respiratory samples.

General Considerations

Hantaviruses are members of the bunyavirus group, which is the largest family of viruses and contains several human pathogens including California encephalitis virus (see Chapter 43). The hantavirus group was first recognized as causing hemorrhagic fevers with renal failure in Asia and Eastern Europe but became much more prominent in the United States when the hantavirus pulmonary syndrome was described in the United States.

  1. Epidemiology

Unlike other bunyaviruses, which have an arthropod vector, hantaviruses spread from mammal to mammal, including humans, by exposure to aerosolized feces, infected urine, or other secretions.

Hantaviruses have been found throughout the world in a variety of rodents and other species. Most of these viruses are associated with hemorrhagic fever, with or without renal failure. In the United States, however, the most notable hantavirus is the Sin Nombre virus, which is associated with the severe pulmonary syndrome. This virus is found in 10–80% of deer mice in rural areas of North America. Spread of virus from rodents to humans is thought to result from intimate contact with the rodent habitat.

  1. Microbiology

These viruses are spherical particles 80–120 nm in diameter. The envelope of the virus contains two glycoproteins and encloses three unique nucleocapsids. The nucleocapsids consist of three separate strands of RNA, the RNA-dependent RNA polymerase, and two nonstructural proteins.

  1. Pathogenesis

In the hemorrhagic fever and hantavirus pulmonary syndromes, the primary lesion is leakage of plasma and erythrocytes through the vascular endothelium. In the former infection these changes are most prominent in the kidney and are accompanied by hemorrhagic necrosis of the kidney; in the latter the primary site of illness is the lung.

Clinical Findings

  1. Signs and Symptoms.Hemorrhagic fevers are characterized by fever, petechial hemorrhages, ecchymoses, epistaxis, hematemesis, melena, and bleeding of gums. Death occurs in ≤ 50% of cases with hemorrhagic phenomena.

Hantavirus pulmonary syndrome (HPS) begins with a prodrome of fever, headache, myalgia, and, often, gastrointestinal symptoms lasting approximately 4–5 days. This is followed by the onset of cough and dyspnea. Tachycardia and tachypnea are present, and hypotension may supervene. The respiratory status may progress to acute respiratory distress syndrome (ARDS) and respiratory failure in several hours. HPS should be especially suspected in healthy young individuals who rapidly develop febrile ARDS and who may have been exposed to rodents.

  1. Laboratory Findings.There are no specific laboratory abnormalities, but hemoconcentration (due to vascular leak) leukocytosis, possibly with left shift, abnormal or increased lymphocytes, thrombocytopenia, or prolonged PTT are seen in the more severe cases. In addition, there is evidence of progressively worsening lung function.
  2. Imaging

Bilateral, diffuse, interstitial pulmonary infiltrates evolve rapidly in patients with HPS.

  1. Differential Diagnosis.Acute, severe pneumonia of multiple causes must be distinguished from HPS. In particular, pneumonia caused by influenza A virus, Legionellaspp., Chlamydia pneumoniae, or Pneumocystis carinii may be similar, but the epidemiology, age of the patient, and other factors provide clues to the etiology.
  2. Complications

The principal complication of hantavirus infection is the severe impairment of lung function.

 

Diagnosis

  1. Culture

Virus may be recovered by inoculation of animals or by cell culture.

  1. Direct detection.Hantavirus RNA can be detected by PCR in clinical specimens from patients with high levels of viremia.
  2. Serology

IgM-specific assays are the main method to rapidly document acute infection. Seroconversion or a fourfold increase in IgG antibody is useful to document recent infection, but cross-reactions within viral genera are common.

Treatment

Ribavirin has been used to treat hantavirus pulmonary syndrome, but its efficacy is not established. Supportive therapy of ARDS is critical to survival.

Prognosis

HPS is fatal in approximately 50% of those who develop clinical illness.

Prevention & Control

Human disease is prevented by interrupting the contact between humans and rodents. Rodent control also minimizes transmission.

COLORADO TICK FEVER

Colorado tick fever, an acute disease characterized by fever, headache, and severe myalgia, was originally described in the nineteenth century and is now believed to be one of the most common tick-borne viral diseases in the United States. Although hundreds of infections occur annually, the exact number is not known because it is not a reportable disease. It is caused by a coltvirus, a member of the reovirus family. This family also includes the rotaviruses, which are discussed in Chapter 37.

  1. Epidemiology

Colorado tick fever has occurred in western and northwestern areas of the United States and western Canada, where the wood tick Dermacentor andersoniis distributed. Ticks acquire the virus by feeding on viremic hosts, and they subsequently transmit the virus in saliva when they feed on a new host. Many ticks have been shown to be infected; however, D andersoni is the predominant vector and the only proven source of human disease. Natural hosts can be one of many mammals, including squirrels, chipmunks, rabbits, and deer. Exposure to ticks is the major risk factor. Human disease is reported during the spring, summer, and fall months. Colorado tick fever is not contagious but has been transmitted by blood transfusion.

  1. Microbiology

The coltvirus virion contains double-stranded RNA and is a spherical isohedron measuring 70–85 nm. There is no envelope, and the virus is resistant to lipid solvents.

  1. Pathogenesis

The viral life cycle includes vertebrates, secondary hosts, and invertebrates (insects). Replication occurs in the cytoplasm of various cells of insect and mammalian origin. Colorado tick fever virus infects hematopoietic cells without severely damaging them. Viremia therefore can persist for weeks or months even after symptomatic recovery.

Clinical Findings

  1. Signs and Symptoms.Acute disease occurs after an incubation period of 3–6 days. Although mild or subclinical infections can occur, most infections are symptomatic with fever, chills, headache, photophobia, myalgia, arthralgia, and lethargy. Neither respiratory nor gastrointestinal symptoms are prominent features. Hemorrhagic disease, confusion, and meningeal signs are unusual but, when they do occur, are more likely in children. Few physical signs are present on examination, but fever, conjunctivitis, lymphadenopathy, hepatosplenomegaly, and maculopapular or petechial rash may be present.
  2. Laboratory Findings.A leukopenia involving both neutrophils and lymphocytes is an important hallmark of the disease. Leukocyte counts are generally less than 4,500/mm3, with a relative lymphocytosis. Despite these findings, disease in children and adults is relatively mild, and uncomplicated recovery can be expected.
  3. Imaging

None reported.

  1. Differential Diagnosis.Colorado tick fever must be differentiated from Rocky Mountain spotted fever, a tick-borne bacterial infection characterized by extensive rash and severe systemic illness.
  2. Complications

There are no serious complications.

Diagnosis

Specific diagnosis can be made by direct detection of viral antigens, viral isolation, or serologic tests. Because the disease is mild and geographically limited, laboratory tests are not broadly available.

  1. Direct Detection.Detection of viral antigen in erythrocytes by immunofluorescence staining has been used as a rapid method of diagnosis.
  2. Viral Isolation.Viral isolation can be performed with serum or plasma during the first few days of disease, before the appearance of neutralizing antibody, and later with the blood clot or washed erythrocytes. Viremia is long lasting and isolation is best accomplished by inoculating suckling mice. Infected mice appear ill in 4–5 days, and viral antigen can be detected by immunofluorescence. Colorado tick fever virus can also be adapted to cell culture, but primary isolation in cell culture is not sensitive.
  3. Serology.A fourfold rise in antibody between the acute and convalescent specimen or the presence of Colorado tick fever virus-specific IgM in either specimen is presumptive evidence of acute or very recent infection. A sharp decline in IgM antibody occurs ~45 days after onset of illness.

Treatment

No specific treatment is available. The disease is generally self-limited, suggesting that supportive care is sufficient. As mentioned, viremia is long lasting, implying that infected patients should not donate blood soon after recovery.

Prognosis

Recovery occurs in > 99% of cases.

Prevention & Control

Prevention includes avoiding tick-infested areas, using protective clothing and tick repellents, and removing ticks before they bite. In contrast with tick-borne rickettsial disease, in which prolonged feeding is required for transmission, the virus from the tick's saliva can enter the bloodstream rapidly. A formalinized Colorado tick fever vaccine has been developed and evaluated but is not practical for use by the general public.

LASSA & OTHER HEMORRHAGIC FEVERS

Lassa fever, with its focus of endemicity in West Africa, is the best known of the arenavirus hemorrhagic fevers. Other agents, such as Junin and Machupo, cause similar syndromes in different geographic areas (Argentina and Bolivia, respectively). Lymphocytic choriomeningitis virus (LCM) is an arenavirus that causes viral meningitis (see Chapter 43).

  1. Epidemiology

Each arenavirus infects specific rodents; for example, the natural host of Lassa fever virus is a small Nigerian rodent. Chronic infection is common in these animals and leads to chronic viremia and virus shedding in saliva, urine, and feces. Infection of humans is primarily from droppings and may occur by way of aerosols, contamination of food, or fomites. Bites are not a usual mechanism of spread. Persistently infected rodents do not usually exhibit illness. Human-to-human infection occurs with Lassa fever virus through contact with infected secretions or body fluids, but this mode of spread rarely if ever occurs with other arenaviruses. Arenaviruses do not require insects for spread. The incubation period for arenavirus infections averages 10–14 days.

  1. Microbiology

Arenaviruses are pleomorphic, helical, and enveloped, with a size of 50–300 nm. They contain RNA in a linear configuration. Replication is in the cytoplasm, with budding from the host cell cytoplasm.

  1. Pathogenesis

Arenaviruses are able to infect macrophages and possibly cause the release of mediators of cell and vascular damage. In certain laboratory animals the clinical severity of arenavirus disease appears to be directly related to the host's immunologic response. The greater the immune (especially T lymphocyte) response, the worse the disease. Whether these mechanisms are operative in human infection is not clear. In patients with the hemorrhagic fever, petechiae and visceral hemorrhage occur, as do liver and spleen necrosis, but not vasculitis.

Clinical Findings

Clinical illness is characterized by fever and coagulopathy. Hemorrhage and shock occur and occasionally cardiac and liver damage. Pharyngitis, diarrhea, and vomiting may be very prevalent, especially in patients with Lassa fever. The diagnosis is suggested by recent travel to endemic areas.

Diagnosis

The diagnosis of arenavirus infections is usually made through serologic tests, although the virus can be recovered by inoculation of blood or cerebrospinal fluid into suckling mice or Vero monkey cells. Throat specimens can yield arenaviruses, as can urine. Substantial risk is present for laboratory workers handling body fluids. Therefore, if the diagnosis is suspected, laboratory personnel should be warned and specimens processed only in facilities specialized for the isolation of contagious pathogens.

Treatment

Only supportive therapy for patients with arenavirus infection is currently available. Uncontrolled studies suggest that ribavirin may be useful for those with Lassa fever.

Prognosis. Death occurs in ≤ 50% of those with Lassa fever and in a smaller percentage among those infected with the other arenaviruses.

Prevention & Control

Prevention of these rodent-borne infections rests on control of the vector's contact with humans. Laboratory-acquired cases can be reduced by processing samples for arenavirus isolation in at least P3 biosafety facilities and not in the usual clinical virology laboratory.

 

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