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 VirusesBackground

Junin Virus : Argentine hemorrhagic fever (AHF)1950’s emergence plagued

the Buenos Aires regionThe peak frequency is during

corn harvesting between March and JuneCase fatality rate of 20%

Machupo Virus: Bolivian hemorrhagic fever (BHF)First documented in 1959

and first isolated in 1963Case fatality rate is 20%

Reservoir

Junin virus Calomys laucha or

Calomys musculinus75% of infected people are

male agricultural workersContaminated 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

BackgroundDiscovered in 1969

when two missionary nurses died in Lassa, Nigeria, W. AfricaIt expands to Guinea,

Liberia, Sierra Leone100 to 300 thousand

cases per year with approx. 5,000 deaths

Case Study

New Jersey, 2004Liberia-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 http://en.wikipedia.org/wiki/Lassa_fever_virus http://en.wikipedia.org/wiki/Machupo_virus http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/lassaf.htm http://www.who.int/mediacentre/factsheets/en/ 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. 317-321

Duschatzky CB; Possetto ML; Talarico LB; García CC; Michis F; Almeida NV; de Lampasona MP; Schuff C; Damonte Ebf. Antiviral chemistry & chemotherapy. [Antivir Chem Chemother] 2005; Vol. 16 (4), pp. 247-51

MMWR: Morbidity & Mortality Weekly Report, 10/1/2004, Vol. 53 Issue 38, p894