PHIDIAS: Pathogen-Host Interaction Data Integration and Analysis System

Table of Contents:

Taxonomy Information
Lifecycle Information
Genome Information
Biosafety Information
Culturing Information
Epidemiology Information
Diagnostic Tests Information
Infected Hosts Information
Phinet: Pathogen-Host Interaction Network
Lab Animal Pathobiology & Management
References
Data Provenance and Curators

Taxonomy Information

Species:
1. Machupo virus (Website 9):
  1. Common Name: Machupo virus
  2. GenBank Taxonomy No.: 11628
  3. Description: BHF is a viral hemorrhagic fever known to be endemic only in Bolivia; first described in 1959, it caused outbreaks in small communities in eastern Bolivia throughout the 1960s. The etiologic agent, Machupo virus, is a member of the family Arenaviridae and is maintained in the rodent C. callosus, the natural reservoir. As with other arenaviruses, infection of the rodent host results in a persistent asymptomatic infection with shedding of virus in urine. Human infections are believed to occur following exposure to the virus in aerosolized rodent urine. A nosocomial outbreak of BHF in Cochabamba in 1971 suggested that person-to-person transmission also may occur by airborne or parenteral routes(MMWR, 1994).

Lifecycle Information

Machupo Virus Information
1. Stage Information:
  1. Virion:
    - Size: Morphologically, arenavirus virions consist of enveloped particles that vary in diameter from approximately 60 to more than 300 nm, with a mean particle size of 92 nm as determined by electron microscopy.
    - Shape: The virions are approximately spherical, enveloped particles that range in diameter from 50 to 300 nm (Southern 1996). The surface of the virion is smooth with T-shaped spikes, composed of viral glycoproteins, extending 7-10 nm from the envelope.

Genome Summary

Genome of Machupo virus
1. Description: The arenavirus genome consists of two single-stranded RNA molecules, designated L and S, that contain essentially nonoverlapping sequence information. There are minor differences in the lengths of the genomic RNA segments for the individual viruses (L approximately 7,200 bases and S approximately 3,400 bases), but the general organization of the viral genomes, based on current sequence information, is well preserved across the virus family(Southern, 1996). The genomic RNA consists of two segments, S (3.4 k) and L (7.2 kb), both of which are arranged in an ambisense orientation. The S segment encodes the nucleocapsid protein (NP) in negative, antimessage sense at the 3'-end and the viral glycoprotein precursor, GP-C in message sense at the 5'-end. The L RNA segment contains the L protein (polymerase) gene at the 3'-end in negative polarity and the zinc-binding (Z) protein at the 5'-end in message polarity. Posttranslational modification of the cell-associated GP-C precursor yields the structural glycoproteins GP-1 (44 kd) and GP-2 (35 kd), which are assembled into a tetrameric virion spike. GP-1 contains determinants that interact with viral receptors and is recognized by neutralizing antibody. GP-2 contains sites that promote acid-dependent membrane fusion necessary for viral entry. The nucleocapsid protein is an internal RNA-binding protein that complexes with genomic RNA(Peters et al., 1996).
2. S Segment(Website 5, Website 4)
  1. GenBank Accession Number: AY129248 AF485260
  2. Size: 3439 bp or 3440 bp in the S segment of Machupo virus(Website 5, Website 4).
  3. Gene Count: 2 genes in the S segment(Peters et al., 1996).
  4. Description: The genomic RNA consists of two segments, S (3.4 k) and L (7.2 kb), both of which are arranged in an ambisense orientation. The S segment encodes the nucleocapsid protein (NP) in negative, antimessage sense at the 3'-end and the viral glycoprotein precursor, GP-C in message sense at the 5'-end(Peters et al., 1996).
3. L Segment
  1. Size: L segment. The genomic RNA consists of two segments, S (3.4 k) and L (7.2 kb), both of which are arranged in an ambisense orientation(Peters et al., 1996).
  2. Gene Count: 2 genes in the L segment(Peters et al., 1996).
  3. Description: The L RNA segment contains the L protein (polymerase) gene at the 3'-end in negative polarity and the zinc-binding (Z) protein at the 5'-end in message polarity(Peters et al., 1996).

Biosafety Information

General biosafety information
1. Level: Like Lassa virus, Junin, Machupo, Guanarito, and Sabia viruses are infectious by aerosol and the human and rodent specimens should be processed with appropriate precautions in BSL 4 laboratories(Buchmeier et al., 2001).
2. Precautions: >. At a minimum, barrier nursing procedures should be implemented and laboratory personnel handling specimens and patient care should wear disposable caps, gowns, shoe covers, surgical gloves, and face masks, (preferably full-face respirators equipped with high-efficiency particulate air (HEPA) filter). Gloves should be disinfected immediately and then replaced if they come in contact with infected blood or secretions(Jahrling, 1989).
3. Disposal: >. All disposable and reusable equipment should be placed directly in a disinfectant solution of sodium hypochlorite, phenolic detergent, or quaternary ammonium compounds. Reusable equipment can then be sterilized(Jahrling, 1989).

Culturing Information

Vero Cell Culture :
1. Description: The best method to isolate Marburg, Ebola, and pathogenic arenaviruses is inoculation of Vero cells, then immunofluorescence or other immunologically-specific testing of inoculated cells for specific viruses at intervals (Jahrling, 1989). Historically, Machupo and Junin viruses were isolated by ic inoculation of newborn hamsters and mice, respectively, but Vero cells are as sensitive and much easier than animals to manage in a P-4 containment. Furthermore, Vero cells permit isolation and identification in 1-5 days, a big advantage over animals, which require 7-20 days of incubation for illness to develop. Co-cultivation of peripheral leukocytes, isolated by hypaque-ficol separation, with susceptible cells (usually Vero) has increased the isolation frequency of Junin virus(Jahrling, 1989).
2. Medium: Clinical specimens and clarified tissue homogenates (usually 10% wt/vol) are diluted in a suitable maintenance medium, such as Eagle's minimal essential medium with Earle's salts and 2% heat-inactivated calf serum(Jahrling, 1989).
3. Note: Vero cells permit isolation and identification in 1-5 days, a big advantage over animals, which require 7-20 days of incubation for illness to develop(Jahrling, 1989). Isolation in cell culture monolayers (Vero, BHK), in combination with immunohistochemical procedures, such as immunofluorescence (IF) or peroxidase-antiperoxidase (PAP), gives positive results in 1 to 3 days(Webb and Maiztegui, 1988). Viremia in man is of low titer, making virus isolation from blood difficult. In addition, virus is rarely isolated by culture of urine or throat swabs. In general, isolation is successful in only one fifth of serologically confirmed or subsequently fatal cases. Virus can be isolated from blood, urine, or throat swabs most frequently between the 7th and 12th day after onset. In fatal cases, virus can be readily isolated from post-mortem spleen and lymph nodes. For virus isolation, newborn hamsters inoculated intracerebrally or intraperitoneally have proved more susceptible than newborn mice of Vero cell culture, and animals appear sick between the 6th and 14th day after inoculation. Although less sensitive than newborn hamsters, daily examination of Vero cell culture by IF may reduce diagnosis time(Shepherd, 1988).

Epidemiology Information:

Outbreak Locations:
1. >. Bolivian hemorrhagic fever (BHF) is caused by Machupo virus. BHF activity has been reported only from the sparsely populated, remote agricultural savannah of northeast Bolivia(Jahrling, 1989).
Transmission Information:
1. From: Calomys callosus(MMWR, 1994, Jahrling, 1989). , To: Human(MMWR, 1994, Jahrling, 1989). , With Destination:Human(MMWR, 1994).
  Mechanism: >. Human infections are believed to occur following exposure to the virus in aerosolized rodent urine(MMWR, 1994).
2. From: Human(MMWR, 1994, Jahrling, 1989). , To: Human(MMWR, 1994, Jahrling, 1989). , With Destination:Human(MMWR, 1994, Jahrling, 1989).
  Mechanism: >. Machupo virus was clearly responsible for a severe nosocomical outbreak of BHF in which all cases were associated with a single index case who had returned from the endemic region(Jahrling, 1989).
Environmental Reservoir:
1. Rodent:
  1. Description: Calomys callosus, the reservoir of Machupo virus, is particularly suited to the cleared areas used for small plots of food crops in the Beni department of Bolivia. This leads to occasional cases of disease among rural residents, principally adult men, who live in or visit these areas. These rodents may also enter small towns in the area, leading to more extensive epidemics that affect everyone(Peters et al., 1996).
  2. Survival: The agents of Bolivian and Argentine hemorrhagic fever can also induce chronic, viremic infection in adult Calomys hosts, but the chronically viremic females are sterile. Neonatally infected reservoir hosts of Machupo and Junin viruses have somewhat retarded growth(Peters et al., 1996).
Intentional Releases:
1. Intentional Release Information:
  1. Emergency Contact: If clinicians feel that VHF is a likely diagnosis, they should take two immediate steps: 1) isolate the patient, and 2) notify local and state health departments and CDC(MMWR, 1988). Report incidents to state health departments and the CDC (telephone {404} 639-1511; from 4:30 p.m. to 8 a.m., telephone {404} 639-2888). Information on investigating and managing patients with suspected viral hemorrhagic fever, collecting and shipping diagnostic specimens, and instituting control measures is available on request from the following persons at Centers for Disease Control (CDC) in Atlanta, Georgia; for all telephone numbers, dial 404-639 + extension: Epidemic Intelligence Service (EIS) Officer, Special Pathogens Branch, Division of Viral Diseases, Center for Infectious Diseases (ext. 1344); Chief, Special Pathogens Branch, Division of Viral Diseases, Center for Infectious Diseases: Joseph B. McCormick, M.D. (ext. 3308); Senior Medical Officer, Special Pathogens Branch, Division of Viral Diseases, Center for Infectious Diseases: Susan P. Fisher-Hoch, M.D. (ext. 3308); Director, Division of Viral Diseases, Center for Infectious Diseases (ext. 3574). After regular office hours and on weekends, the persons named above may be contacted through the CDC duty officer (ext. 2888)(MMWR, 1988).
  2. Delivery Mechanism: >. The VHF agents are all highly infectious via the aerosol route, and most are quite stable as respirable aerosols. This means that they satisfy at least one criterion for being weaponized, and some clearly have the potential to be biological warfare threats. Most of these agents replicate in cell culture to concentrations sufficiently high to produce a small terrorist weapon, one suitable for introducing lethal doses of virus into the air intake of an airplane or office building. Some replicate to even higher concentrations, with obvious potential ramifications. Since the VHF agents cause serious diseases with high morbidity and mortality, their existence as endemic disease threats and as potential biological warfare weapons suggests a formidable potential impact on unit readiness. Further, returning troops may well be carrying exotic viral diseases to which the civilian population is not immune, a major public health concern(Website 3).
  3. Containment: >. Patients with VHF syndrome generally have significant quantities of virus in their blood, and perhaps in other secretions as well (with the exceptions of dengue and classic hantaviral disease). Well-documented secondary infections among contacts and medical personnel not parenterally exposed have occurred. Thus, caution should be exercised in evaluating and treating patients with suspected VHF syndrome. Over-reaction on the part of medical personnel is inappropriate and detrimental to both patient and staff, but it is prudent to provide isolation measures as rigorous as feasible. At a minimum, these should include the following: stringent barrier nursing; mask, gown, glove, and needle precautions; hazard-labeling of specimens submitted to the clinical laboratory; restricted access to the patient; and autoclaving or liberal disinfection of contaminated materials, using hypochlorite or phenolic disinfectants. For more intensive care, however, increased precautions are advisable. Members of the patient care team should be limited to a small number of selected, trained individuals, and special care should be directed toward eliminating all parenteral exposures. Use of endoscopy, respirators, arterial catheters, routine blood sampling, and extensive laboratory analysis increase opportunities for aerosol dissemination of infectious blood and body fluids. For medical personnel, the wearing of flexible plastic hoods equipped with battery-powered blowers provides excellent protection of the mucous membranes and airways(Website 3).

Diagnostic Tests Information

Organism Detection Test:
1. Electron Microscopy :
  1. Description: When the identity of a VHF agent is totally unknown, isolation in cell culture and direct visualization by electron microscopy, followed by immunological identification by immunohistochemical techniques is often successful(Website 3).
2. Immunofluorescence :
  1. Description: Serological diagnosis of Bolivian hemorrhagic fever is made by immunofluorescence, complement fixation, or plaque reduction neutralization. However, appearance of antibodies is relatively late by all tests: 14 days at the earliest. In practice, it is necessary to test for seroconversion between 40 and 60 days after the onset (Shepherd, 1988). Although less sensitive than newborn hamsters, daily examination of Vero cell culture by IF may reduce diagnosis time(Shepherd, 1988).
3. Intracerebral or Intraperitoneal Inoculation :
  1. Description: For virus isolation, newborn hamsters inoculated intracerebrally or intraperitoneally have proved more susceptible than newborn mice or Vero cell culture, and animals appear sick between the 6th and 14th day after inoculation. Although less sensitive than newborn hamsters, daily examination of Vero cell culture by IF may reduce diagnosis time(Shepherd, 1988).
Immunoassay Test:
1. Complement Fixation :
  1. Description: The complement fixation (CF) test is rarely used now, although historically it was the method of choice for detection and presumptive identification of the arenaviruses. The CF test was supplanted by immunofluorescence procedures which became generally accepted(Website 3).
2. Antigen capture ELISA :
  1. Description: Antigen capture ELISA allowed detection of viral antigen in blood, serum, or tissue homogenates. These tests could be used in acute diagnosis of patients suspected of Junin, Machupo. Sabia, and Guanarito and are often the first available diagnostic result in rapidly fatal cases when patients died before antibody appearance(Peters et al., 1996).
3. Elisa with IgG linked with Horeseradish Peroxidase :
  1. Description: Conditions for ELISA by using IgG linked with horseradish peroxidase have been developed for the detection of 6 arenaviruses (Machupo, Junin, Tacaribe, Amapari, LCM and Tamiami). This method allows the detection of arenavirus antigens in various materials; organs and blood in affected animals and infected cell culture fluids. It shows higher sensitivity and allows an earlier detection of virus-specific antigens as compared with the CF test(Ivanov et al. 1981).
4. Plaque Reduction Neutralization :
  1. Description: Neutralization tests (Nt) for these viruses vary in efficacy; depending on the virus. Neutralization tests range from very sensitive and reliable (e.g. Junin and Machupo), through moderately insensitive but reliable (Lassa and LCM), to totally unreliable (Marburg and Ebola). The common denominator in all Nt tests is measurement of inhibition of viral replication by reaction with immune serum(Jahrling, 1989). For New World arenaviruses (Junin and Machupo), the usual test is a plaque reduction Nt using Vero cells and the serum dilution-constant virus format. The serum dilution calculated by (probit analysis) to reduce the control number of plaques by 50% (PRN-50) is usually taken as the endpoint, although some laboratories use 80% reduction (PRN-80). The PRN-80 is used to distinguish Junin virus from Machupo virus(Jahrling, 1989).
5. Indirect Immunofluorescence Antibody (IIF) Test :
  1. Description: The IIF test is clearly the method of choice in most laboratories for detecting recent infections with Marburg, Ebola, and the arenaviruses. Antibodies measured by the IFA test are usually the first to appear, often becoming detectable within the first few days of hospitalization for Lassa virus, within 10 days of onset for Marburg and Ebola viruses, and somewhat later for Junin and Machupo viruses. Presence of specific IgM antibodies or a rising IFA titer is a presumptive diagnosis of acute infection. IgM antibodies measure by IIF decline to undetectable titers within several months, while IgG antibodies persist at least several years(Jahrling, 1989).

Infected Hosts Information

Human
1. Taxonomy Information:
  1. Species:
    1. Homo sapiens (Website 8):
      - Common Name: Homo sapiens
      - GenBank Taxonomy No.: 9606
      - Description: Human infection with arenaviruses is incidental to the natural cycle of the viruses and occurs when an individual comes into contact with the excretions or materials contaminated with the excretions of an infected rodent, such as ingestion of contaminated food, or by direct contact of abraded or broken skin with rodent excrement. Infection can also occur by inhalation of tiny particles soiled with rodent urine or saliva (aerosol transmission). The types of incidental contact depend on the habits of both humans and rodents. For example, where the infected rodent species prefers a field habitat, human infection is associated with agricultural work. In areas where the habitat of rodent species includes human homes or other buildings, infection occurs in domestic settings(Website 7).
2. Infection Process:
  1. Infectious Dose: 1-10 organisms(Franz et al., 1997),
  2. Description: Human infection with arenaviruses is incidental to the natural cycle of the viruses and occurs when an individual comes into contact with the excretions or materials contaminated with the excretions of an infected rodent, such as ingestion of contaminated food, or by direct contact of abraded or broken skin with rodent excrement. Infection can also occur by inhalation of tiny particles soiled with rodent urine or saliva (aerosol transmission). The types of incidental contact depend on the habits of both humans and rodents. For example, where the infected rodent species prefers a field habitat, human infection is associated with agricultural work. In areas where the habitat of the rodent species includes human homes or other buildings, infection occurs in domestic settings(Website 7),
3. Disease Information:
  1. Bolivian hemorrhagic fever :
    1. Incubation: >, 1-2 weeks(MMWR, 1994),
    2. Prognosis:
    3. Symptom Information :
      - Syndrome -- Bolivian Hemorrhagic Fever :
        
        Description: Following an incubation period of 1-2 weeks, patients infected with Machupo virus may develop an influenza-like illness with fever, malaise, and fatigue followed by the onset of headache, dizziness, myalgias, and severe lower back pain. Prostration, abdominal pain, anorexia, tremors, and hemodynamic instability may be followed by hemorrhagic manifestations, including bleeding from the oral and nasal mucosa and the gastrointestinal, genitourinary, and bronchopulmonary tracts(MMWR, 1994).
        
        Observed:
        In 1960, 21 cases of adult males were reported during the greatest agricultural activity from April to September. Since then until 1964, a large outbreak developed in San Joaquin, Orobayaya and the surrounding area. This epidemic affected more than 500 people with a fatality rate of 18%. Cases occurred in all persons independently of age, sex, and occupation. The epidemic curve began to rise at the end of the rainfall season, and the largest number of cases was reported during the dry season. A rodent eradication program was instituted in the endemoepidemic area from May to July of 1964 and the number of BHF cases dropped almost simultaneously. The last cases were reported in November of 1964(Vainrub and Salas, 1994), No outbreaks were recognized between 1971 and 1994. In the summer of 1994 an outbreak involving 10 people occurred in northeastern Bolivia(Website 1),
        
        Symptom -- Machupo Hemorrhagic Fever :
        
        Description: Patients infected with Machupo virus may develop an influenza-like illness with fever, malaise, and fatigue followed by the onset of headache, dizziness, myalgias, and severe lower back pain. Prostration, abdominal pain, anorexia, tremors, and hemodynamic instability may be followed by hemorrhagic manifestations, including bleeding from the oral and nasal mucosa and the gastrointestinal, genitourinary, and bronchopulmonary tracts(MMWR, 1994).
        
        Observed:
        Normal inhabitants of the endemic area have antibody prevalence of 0.1% to 3% and household contacts have 10.5%(Peters et al., 1996),
      - Symptom -- Fever :
        
        Description: Fever(Vainrub and Salas, 1994, MMWR, 1994).
      - Symptom -- Malaise :
        
        Description: Malaise(MMWR, 1994).
      - Symptom -- Fatigue :
        
        Description: Fatigue(MMWR, 1994).
      - Symptom -- Arthralgia :
        
        Description: Arthralgia(Vainrub and Salas, 1994).
      - Symptom -- Headache :
        
        Description: Headache(Vainrub and Salas, 1994, MMWR, 1994).
      - Symptom -- Dizziness :
        
        Description: Dizziness(MMWR, 1994).
      - Symptom -- Myalgia :
        
        Description: Myalgia(Vainrub and Salas, 1994, MMWR, 1994).
      - Symptom -- Lower back pain :
        
        Description: Severe lower back pain(MMWR, 1994).
      - Symptom -- Prostration :
        
        Description: Prostration(MMWR, 1994).
      - Symptom -- Abdominal pain :
        
        Description: Abdominal pain(MMWR, 1994).
      - Symptom -- Anorexia :
        
        Description: Anorexia(MMWR, 1994).
      - Symptom -- Tremors :
        
        Description: Tremors(MMWR, 1994).
      - Symptom -- Hemodynamic instability :
        
        Description: Hemodynamic instability(MMWR, 1994).
      - Symptom -- Vomiting :
        
        Description: Vomiting(Vainrub and Salas, 1994).
      - Symptom -- Diarrhea :
        
        Description: Diarrhea(Vainrub and Salas, 1994).
      - Symptom -- Petechiae :
        
        Description: Petechiae(Vainrub and Salas, 1994).
      - Symptom -- Bleeding :
        
        Description: Bleeding. Hemorrhagic manifestations include bleeding from the oral and nasal mucosa and the gastrointestinal, genitourinary, and bronchopulmonary tracts(Vainrub and Salas, 1994, MMWR, 1994).
      - Symptom -- Encephalopathy :
        
        Description: Encephalopathy(Vainrub and Salas, 1994).
      - Symptom -- Erythema :
        
        Description: Erythema(Vainrub and Salas, 1994).
      - Symptom -- Facial edema :
        
        Description: Facial edema(Vainrub and Salas, 1994).
      - Symptom -- Shock :
        
        Description: Shock(Vainrub and Salas, 1994).
      - Symptom -- Leukopenia :
        
        Description: Leukopenia(Vainrub and Salas, 1994).
      - Symptom -- Thrombocytopenia :
        
        Description: Thrombocytopenia(Vainrub and Salas, 1994).
    4. Treatment Information:
      - Supportive therapy : Supportive therapy is important in the management of patients with arenal viral hemorrhagic fevers. Avoidance of travel and general trauma, gentle sedation and pain relief with conservative doses of opiates, the usual precautions for patients with bleeding diatheses (e.g., avoidance of intramuscular injections or acetylsalicylic acid), and careful maintenance of hydration are indicated. Bleeding should be managed by platelet transfusions and factor replacement, as indicated by clinical judgment and laboratory studies(Peters et al., 1996).
        
        Complication: Management of shock is difficult. Modest increases in hematocrit indicate a generalized vascular permeability problem, but not of the magnitude seen in diseases such as hantavirus pulmonary syndrome. Nevertheless, vigorous infusion of crystalloid carries a high risk of pulmonary edema. Cautious administrations of fluids and early use of pressors is indicated. Because of the implications of the low cardiac output seen in the Pichinde guinea pig model of arenaviral hemorrhagic fever and clinical experience with human disease, careful monitoring is important and Swan-Ganz catheterization is desirable(Peters et al., 1996).
      - Ribavirin : We had the opportunity to offer intravenous ribavirin to two of three patients with this potentially life-threatening infection. One patient with laboratory-confirmed Machupo virus infection who received ribavirin recovered without sequelae, as did a second patient with suspected BHF whose epidemiological and clinical features were similar to those of the first patient(Kilgore et al., 1997).
        
        Contraindicator: >. Although ribavirin should not be used when renal impairment is present, it may be necessary for severe disease in which the potential benefit may outweigh the risks. Ribavirin is contraindicated in pregnancy(Website 2).
        
        Complication: >. Anemia (most commonly), insomnia, depression, irritability, and suicidal behavior have been reported with PO administration; with IV administration, reversible suppression of erythropoiesis, mild hemolysis, and mild direct hyperbilirubinemia are expected and generally manageable(Website 2).
        
        Success Rate: The clinical and laboratory data obtained from the treatment of these two patients suggest that intravenous ribavirin may be active against Machupo virus following natural infection in humans(Kilgore et al., 1997).
      - Convalescent immune plasma : Treatment of BHF employs supportive measures. Although uncontrolled trials have used convalescent immune plasma from survivors of BHF, evaluation of the effectiveness of this therapy has been limited by the lack of plasmapheresis capability and availability of qualified donors(MMWR, 1994). During the BHF epidemics of the 1960s, convalescent-phase immune plasma from survivors of BHF was administered to selected patients infected with Machupo virus. However, there is currently a paucity of survivors of BHF who can donate immune plasma, and there is no active program for collection and storage of BHF immune plasma(Kilgore et al., 1997).
4. Prevention:
  1. Rodent control
    - Description: Trapping rodents was shown to stop disease transmission in towns. Indeed, no cases of BHF were recognized after 1975 until 1993, when a case was noted. These infections were acquired outside towns(Peters et al., 1996),
    - Efficacy:
      - Rate: Since C. callosus was frequently found in domestic and peridomestic environments, rodent control measures (e.g., trapping, poisoning) resulted in an immediate reduction in the number of C. callosus and control of BHF outbreaks; an epidemic in 1964 ended after 2 weeks of continuous trapping for C. callosus in homes of the affected community. Rodent control programs became a new priority for health officials in Bolivia, and active interventional programs were carried out for many years by survivors of past BHF epidemics known to be immune to Machupo virus(Kilgore et al., 1995).
      - Duration: More than 1000 cases of BHF were recorded from 1960 -1964, but less than 200 in the past 10 years(Mercado, 1975). From 1973 to 1992, no cases of BHF were reported, possibly because of effective control of rodent reservoir populations(Kilgore et al., 1995).
  1. Barrier nursing
    - Description: Prevention of community wide epidemics through rodent control programs may be combined with the application of barrier precautions (e.g., gloves, masks) in hospitals or clinics to minimize secondary person-to-person transmission of Machupo virus(Kilgore et al., 1995), Strict barrier-nursing techniques should be enforced: all persons entering the patient's room should wear disposable gloves, gowns, masks, and shoe covers. Protective eye wear should be worn by persons dealing with disoriented or uncooperative patients or performing procedures that might involve the patient's vomiting or bleeding (for example, inserting a nasogastric tube or an intravenous or arterial line). Protective clothing should be donned and removed in the anteroom. Only essential medical and nursing personnel should enter the patient's room and anteroom. Isolation signs listing necessary precautions should be posted outside the anteroom(MMWR, 1988),
  1. Vaccine Candid #1
    - Description: Future efforts to control BHF may benefit from recent experience in neighboring Argentina where ongoing work has led to the control of Argentine hemorrhagic fever (AHF), caused by Junin virus, an arenavirus genetically related to Machupo virus. Extensive study of AHF by Maiztegui, Enria, and colleagues has provided new insights into the epidemiology, pathogenesis, treatment, and control of this disease and has led to an effective Candid #1 vaccine against Junin virus as well as phase 2 clinical trials that suggest ribavirin may be effective in patients with AHF. The use of an effective vaccine against AHF and evidence for its cross-protection against Machupo virus suggest that vaccination may play a role in the prevention of BHF for persons at highest risk, such as workers who trap rodents for control programs(Kilgore et al., 1995),
5. Model System:
  1. Rhesus monkey
    1. Model Host: .
      Rhesus monkey(Webb et al., 1975),
    2. Model Pathogens: (Webb et al., 1975).
    3. Description: The disease produced by Machupo virus in rhesus monkeys resembled even more closely that seen in humans. Haemorrhagic signs and many of the pathological changes recorded for Bolivian haemorrhagic fever were observed. Rhesus monkeys are currently being used as the definitive host for work on Machupo virus vaccine(Webb et al., 1975),
  1. Marmoset
    1. Model Host: .
      Marmoset, Saguinus geoffroyi(Webb et al., 1975),
    2. Model Pathogens: (Webb et al., 1975).
    3. Description: Marmosets developed anorexia, tremors, and clinical shock, and succumbed 8-20 days after inoculation(Webb et al., 1975),
  1. African green monkey
    1. Model Host: .
      African green monkey(McLeod et al., 1978),
    2. Model Pathogens: (Webb et al., 1975).
    3. Description: Gross and microscopic pathological findings are presented for an African green monkey model of fatal Bolivian hemorrhagic fever. Six animals were inoculated with 1,000 plaque-forming units of Machupo virus, the etiological agent of Bolivian hemorrhagic fever. Five of the monkeys died within 13 days with signs of fever, anorexia, shock, and hemorrhage. The sixth monkey survived until the 24th day and died with signs of central nervous system disease. Gross lesions in the five monkeys that die in the acute stage included hepatic necrosis, necrotic enteritis, bronchopneumonia, and hemorrhages in the subcutis, lungs, intestine, liver, and lymph nodes. Microscopically, necrosis was consistently seen in liver, intestine, skin, oral cavity, and adrenal cortex. Acute thrombosis was observed in four monkeys, in blood vessels of the intestine, lung and choroid of the brain. Gram-negative bacteria were seen in many tissues, suggesting terminal bacteremia. The sixth monkey was emaciated and had bronchopneumonia, but did not have the necrotic hepatic and enteric lesions observed in the other five monkeys. The significant microscopic lesions in this monkey included encephalomyelitis, ganglionitis, and bronchopneumonia(McLeod et al., 1978),
  1. Guinea pig
    1. Model Host: .
      Guinea pig, Strain C-13(Webb et al., 1975),
    2. Model Pathogens: (Webb et al., 1975).
    3. Description: Guinea pig disease was nondescript; there was little or no viraemia and no evidence of haemorrhage(Webb et al., 1975),
  1. Hamster
    1. Model Host: .
      Hamster(Webb et al., 1975),
    2. Model Pathogens: (Webb et al., 1975).
    3. Description: Suckling hamsters and mice were susceptible to Machupo virus infection with fatal outcome; adult hamsters and mice developed N antibody(Webb et al., 1975),
  1. Mouse
    1. Model Host: .
      Mouse(Webb et al., 1975),
    2. Model Pathogens: (Webb et al., 1975).
    3. Description: Suckling hamsters and mice were susceptible to Machupo virus infection with fatal outcome; adult hamsters and mice developed N antibody(Webb et al., 1975),
Rodent
1. Taxonomy Information:
  1. Species:
    1. Calomys callosus (Website 6):
      - Common Name: Calomys callosus
      - GenBank Taxonomy No.: 56210
      - Description: The etiologic agent, Machupo virus, is a member of the family Arenaviridae and is maintained in the rodent Calomys callosus, the natural reservoir. As with other arenaviruses, infection of the rodent host results in a persistent asymptomatic infection with shedding of virus in urine(MMWR, 1994).

Phinet: Pathogen-Host Interaction Network

Not available for this pathogen.

Lab Animal Pathobiology & Management

References:

Buchmeier et al., 2001: Buchmeier MJ, Bowen MD, Peters CJ. Arenaviridae: The viruses and their replication. 1635-1668. In: . Field's Virology Fourth Edition Volume 2. 2001. Lippincott Williams and Wilkins, Philadelphia Pa.

Franz et al., 1997: Franz DR, Jahrling PB, Friedlander AM, McClain DJ, Hoover DL, Bryne WR, Pavlin JA, Christopher GW, Eitzen EM Jr. Clinical recognition and management of patients exposed to biological warfare agents. JAMA. 1997; 278(5); 399-411. [PubMed: 9244332].

Ivanov et al. 1981: Ivanov AP, Bashkirtsev VN, Tkachenko EA. Enzyme-linked immunosorbent assay for detection of arenaviruses. Arch Virol. 1981; 67(1); 71-74. [PubMed: 7016080].

Jahrling, 1989: Jahrling PB. Arenaviruses and filoviruses. 857-891. In: . 6th Edition. Diagnostic procedures for viral, rickettsial, and chlamydial infections. 1989. American Public Health Association, Inc., Washington DC.

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Website 1: Viral Hemorrhagic Fever (VHF): Current, comprehensive information on pathogenesis, microbiology, epidemiology, diagnosis, treatment, and prophylaxis

Website 2: Viral Hemorrhagic Fevers

Website 3: Viral Hemorrhagic Fevers

Website 4: Machupo virus strain Carvallo segment S, complete sequence

Website 5: Machupo virus strain Carvallo segment S, complete sequence

Website 6: Calomys callosus

Website 7: Arenaviruses

Website 8: Homo sapiens

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