Viral Hemorrhagic Fevers: Lassa, Machupo, Junin Remy Schneider Jazmin Jerez

Arenavirus Structure Single-stranded, bi- segmented RNA genome Large segment (7200nt), small one (3500nt) Lipid envelope with 8- 10nm club-shaped projections

South American Fever Viruses Background Junin Virus : Argentine hemorrhagic fever (AHF) 1950’s emergence plagued the Buenos Aires region The peak frequency is during corn harvesting between March and June Case fatality rate of 20% Machupo Virus: Bolivian hemorrhagic fever (BHF) First documented in 1959 and first isolated in 1963 Case fatality rate is 20%

Reservoir Junin virus Calomys laucha or Calomys musculinus 75% of infected people are male agricultural workers Contaminated by inhalation of infected aerosols or from rodents caught in mechanical harvesters Machupo virus Calomys callosus

Symptoms Junin/Machupo virus: Incubation 7-16 days with slow onset of symptoms First symptoms: fever, malaise, headache, muscular pains, anorexia, nausea and vomiting Between third and fifth day: dehydration, hypotension, infrequent urination, bradycardia Hemorrhagic phase: Begins with petechiae (blood spots) on upper trunk and oral mucosa Hemorrhaging starts from nose, gums, stomach and intestines where severe blood loss results in hypotensive shock and neurological crisis

Remedies Junin Immune plasma therapy Herbal: NDGA-compound in Larra divaricata leaf resin & aromatic plant oils from Argentina Candid 1, live-attenuated vaccine Induces neutralizing antibody response Developes virus-specific antibody-dependant cellular cytotoxicity Machupo immune plasma therapy from survivors Ribavirin Candid 1 gives some protection from BHF

Lassa Fever Virus Background Discovered in 1969 when two missionary nurses died in Lassa, Nigeria, W. Africa It expands to Guinea, Liberia, Sierra Leone 100 to 300 thousand cases per year with approx. 5,000 deaths

Case Study New Jersey, 2004 Liberia-born US resident travels to West Africa. He begins to feel feverish, with chills, severe soar throat, diarrhea, and back pain. He travels back to Newark, is then admitted to a hospital in Trenton where he eventually dies.

Primary Means of Diagnosing Arenaviruses

Reservoir/Transmission Multimammate rat (Mastomys natalensis) High breed frequency Virus shed in urine and feces Instinctual scavengers Person to person contact through exchange of bodily fluids only Nosocomial transmission

Symptoms Incubation period of 6-21 days 80% of human infections are asyptomatic Onset is slow: fever, weakness, & malaise Few days: headache, pharyngitis, muscle pain, retrostinal & abdominal pain, nausea, vomiting, conjunctivitis, diarrhea, cough, & proteinuria Severe cases: facial swelling, lung cavity fluid, hemorrhaging, hyopotension, Neurological problems: tremors, encephalitis, hair loss, gait disturbance, deafness 95% deathrate among pregnant women & spontaneous abortion

Remedies Antiviral therapy (Ribavirin) Acts via lethal mutagenesis 1989 study: Rhesus monkeys injected with mopeia & vaccinia (V-LSGPC) viruses and escaped death Non-Specific control: fluid replacement (electrolyte balance), blood transfusion, fighting of hypotension Hemmorrhaging treated with clotting factor and/or platelet repacement Promising vaccine Developed by USAMDRID (2005) Attentuated recombinant stomatitis virus vector expressing the Lassa viral glycoprotein

Prevention Nosocomial: Complete equipment sterilization & protective clothing House to house rodent trapping Better food storage & hygiene Cautious handling of rodent if used as food source

References m m S. P. Fisher-Hoch; J. B. McCormick; D. Auperin; B. G. Brown; M. Castor; G. Perez; S. Ruo; A. Conaty; L. Brammer; S. Bauer. Proceedings of the National Academy of Sciences of the United States of America, Vol. 86, No. 1. (Jan. 1, 1989), pp Duschatzky CB; Possetto ML; Talarico LB; Garc í a CC; Michis F; Almeida NV; de Lampasona MP; Schuff C; Damonte Ebf. Antiviral chemistry & chemotherapy. [Antivir Chem Chemother] 2005; Vol. 16 (4), pp Duschatzky CBPossetto MLTalarico LBGarc í a CCMichis F Almeida NVde Lampasona MPSchuff CAntiviral chemistry & chemotherapy. MMWR: Morbidity & Mortality Weekly Report, 10/1/2004, Vol. 53 Issue 38, p894