Chapter 9:

Viral Agents of Human Disease: Biosafety Concerns

This chapter explores the hazards associated with handling biosamples containing viruses and the
resulting occupational exposure risks. It covers basic virology concepts, clinical syndromes of
viral infections, and specific attention to viral pathogens with work-acquired infection risks. The
safety challenges posed by modern biotechnologies are also discussed.
1. Historical Context:Viruses discovered as major causes of epidemics since the early
1900s.Emerging infections often linked to evolving, previously unrecognized, or human-
induced environmental changes.
2. Viral Infections:Acute viral infections may result in various manifestations, from
asymptomatic to severe multiorgan illnesses.Severity influenced by viral factors
(virulence), exposure amount, entry route, and host factors.
3. Laboratory-Associated Infections (LAIs):Historical surveys show viruses pose
significant risks.Arboviruses, transmitted by arthropod vectors, particularly
risky.Exposure sources include infectious aerosols, animal handling, and accidents.
4. Virus Taxonomy:Viruses classified by the International Committee on Taxonomy of
Viruses (ICTV) based on genome type, replication strategy, and virion structure.Diversity
exemplified by RNA viruses' rapid evolution.
5. Arboviral Epidemiology:Arboviruses, transmitted by arthropods, vary in transmission,
epidemiology, and clinical manifestations.Dengue and Zika viruses illustrate the complex
epidemiology and disease burden associated with arboviruses.
6. Infectious and Lethal Doses: Biosafety with Viruses
 Discoveries and Risks:Viruses discovered causing major diseases in the 1900s.New
infections often linked to environmental changes and human activities.
 Virus Effects:Infections can range from no symptoms to severe illnesses.Severity
depends on virus strength, exposure amount, and host factors.
 Lab Dangers:Lab studies show viruses pose risks, especially arboviruses transmitted by
insects.Exposure sources include aerosols, animal contact, and accidents.
 Virus Types:Viruses classified by characteristics like genome type.RNA viruses evolve
rapidly, making them diverse.
 Arbovirus Challenges:Diseases like dengue and Zika show complex patterns due to
arthropod transmission.Continuous risk evaluation needed for evolving viruses.
 Doses and Risks:Infectious dose is the amount causing infection; lethal dose causes host
death.Important for setting safety levels in labs.
  Risk Matrix:Risk assessment considers how likely an event is and its consequences.
Matrix helps categorize work risks based on virus properties, procedures, and severity.
 Gene Editing Risks:CRISPR/Cas9 technology makes genome changes easier.Risk
matrix useful for assessing risks in gene editing, especially with evolving technologies.
 Conclusion:Understanding virus risks helps labs make safe decisions.Continuous
evaluation needed, especially with advancing technologies.

Clinical Manifestations of Viral Diseases: Biosafety Concerns

Introduction:Understanding clinical consequences is vital for assessing risks in handling known
and unknown viruses.Diagnostic specimens from undiagnosed patients pose significant risks,
necessitating vigilance.
Incubation Period:Varies (3 to 15 days), longer for some viruses (hepatitis B/C,
rabies).Incubation period may shorten with increased virus inoculation.
Clinical Manifestations by Syndrome
1. Fever and Rash:Hallmark of many viral infections.Differentiating signs may occur later
in the clinical course.
2. Acute Neurologic Disorders:Include meningitis and encephalitis.Various viruses cause
meningoencephalitis.
3. Respiratory:Upper respiratory syndromes, pneumonia.Severe cases can lead to acute
respiratory distress syndrome.
4. Hepatitis:Classic phases: incubation, prodromal, icteric, convalescent.Symptoms include
fever, jaundice, dark urine.
5. Acute Gastroenteritis:Nausea, vomiting, abdominal pain, diarrhea.Self-limited, lasting 2-
4 days.
6. Hemorrhagic Fever:Characterized by fever, systemic symptoms, coagulopathy.Examples:
Dengue, Ebola, Marburg.
7. Mononucleosis Syndrome:Caused by viruses like EBV, CMV, HIV.Flu-like symptoms,
enlarged liver/spleen, prolonged fatigue.
Viremia and Clinical Illness Day
 Peak viremia indicates highest-risk period for exposure from clinical specimens.
Post accident Management
 Contingency planning crucial.
 Medical assessment of individuals before lab work.
 Prompt recognition of exposure, thorough clinical follow-up.
Selected Viral Pathogens Producing LAIs
1. Adenoviridae:DNA-containing viruses, 49 human serotypes.LAIs reported; effective
vaccine for serotypes 4 and 7.
2. Arenaviridae:Enveloped viruses with RNA segments.Example: LCMV - associated with
rodent contact, aerosol transmission.Case: Sabia virus infection – lab-acquired, treated
with ribavirin.

Post accident Management: B Virus Exposure

CDC Recommendations:
1. Institutions must be prepared to handle patients with suspected B virus exposure.
2. Patients should have immediate access to a local medical consultant knowledgeable about
B virus.
3. Thoroughly cleanse the wound.
4. Obtain serum samples and cultures for serology and viral isolation from both patient and
monkey.
5. Consider initiation of antiviral therapy based on exposure risk.
6. Management is controversial; consult CDC for assistance.
7. Refer to the B Virus Research and Resource Laboratory for diagnostic resources.
Orthomyxoviridae: Influenza Viruses
General Information:
1. Family consists of enveloped viruses with segmented, single-stranded, negative-stranded
RNA genome.
2. Four genera: Influenzavirus A, B, C, and D.
3. Influenza A, B, C cause significant respiratory morbidity; undergo genetic shift and drift.
4. Humans are the reservoir, but infections occur in various animals.
5. Laboratory workers at risk of Laboratory-Acquired Infection (LAI).
LAI and Postaccident Management:
1. Workers at risk via aerosol and fomite transmissions.
2. Vaccination recommended annually; FDA licensed avian H5N1 vaccine available.
3. Seek immediate medical attention post-exposure.
4. Antivirals (neuraminidase inhibitors, M2 blockers) effective if promptly administered.
 5. Contagious; avoid contact with vulnerable populations.
6. Provide virus modification details for exposed worker's medical management.
Paramyxoviridae: Paramyxoviruses
General Information:
1. Enveloped, negative-stranded RNA viruses; two subfamilies: Paramyxovirinae,
Pneumovirinae.
2. Important animal/human pathogens: Newcastle disease, mumps, measles, RSV, etc.
3. LAIs associated with Newcastle disease, Sendai virus, mumps, measles, RSV.
LAI and Postaccident Management:
1. Prevent Newcastle disease by immunization and use of appropriate protective equipment.
2. Vaccinate personnel against mumps and measles; monitor and remove symptomatic
individuals.
3. No licensed RSV vaccine; confirm potential LAIs, monitor symptomatic personnel.
Picornaviridae: Enteroviruses, Rhinovirus, HAV
General Information:
1. Small, non-enveloped viruses with single-stranded RNA; six genera.
2. Human pathogens: Enterovirus, rhinovirus, HAV.
3. Enteroviruses and HAV transmitted orally; rhinovirus transmitted by aerosol.
LAI and Postaccident Management:
1. Enterovirus infections range from asymptomatic to severe illnesses; monitor and manage
symptoms.
2. Rhinovirus causes common cold; manage symptoms.
3. HAV produces acute viral hepatitis; monitor liver enzymes, jaundice.

Picornaviridae:
 Responsible for many Laboratory-Acquired Infections (LAIs).
 Examples: Mengo encephalomyocarditis virus, coxsackievirus, HAV, poliomyelitis virus.
 Postaccident management involves a thorough exam, clinical follow-up, and vaccination
for personnel working with poliovirus or HAV.
Poxviridae:
  Family with single linear double-stranded DNA.
 Subfamilies: Entomopoxvirinae (insect viruses) and Chordopoxvirinae (animal viruses).
 Example: Monkeypox (Orthopoxvirus), Tanapox virus (Yatapoxvirus).
 Zoonotic transmission possible; monkeypox has been implicated in outbreaks.
 Yaba monkey tumorvirus (Yatapoxvirus) reported in non-human primates.
 Orf is a parapoxvirus causing infections in sheep, goats, and humans through contact with
infected animals.
LAI with Vaccinia Virus:
 Documented infections in laboratory workers.
 Risks include needlestick injuries.
 Vaccination is crucial; booster vaccines are recommended.
 Proper evaluation and vaccination can reduce severity.
Retroviridae:
 Family with RNA genome; transcribes into DNA upon host cell entry.
 Genera: Alpharetrovirus, Betaretrovirus, Gammaretrovirus, Deltaretrovirus,
Epsilonretrovirus, Lentivirus, and Spumavirus.
 Examples: HIV (LAI risk in healthcare workers), SIV (lentivirus in non-human primates).
 Postexposure management involves thorough cleaning, chemoprophylaxis, and
diagnostic testing.
Rhabdoviridae:
 Enveloped, negative-stranded RNA viruses.
 Example: Rabies virus (LAI through bites or aerosol exposure).
 Postexposure management includes a comprehensive exam and rabies treatment.
Togaviridae:
 Positive-stranded RNA viruses with Alphavirus and Rubivirus genera.
 Examples: Chikungunya, VEE, Rubella virus.
 Alphaviruses responsible for numerous LAIs.
 Rubella vaccine available; workers should be vaccinated.
Genetically Engineered Viruses:
 GOF (Gain-of-Function) research: Altered viruses for research purposes.
 Concerns about dual-use potential and accidental release.
 Moratoriums and oversight recommendations for GOF research.
 CRISPR/Cas9 technology and viral-vectored genome editing can efficiently edit viral
genomes.

Conclusion
 Risk Recognition: Viral infections pose severe risks, demanding a well-coordinated
program for effective management.
 Key Steps:
 Assessment: Understand virus risks and transmission pathways.
 Prevention: Implement safety protocols and protective measures.
 Guidelines: Strictly follow biosafety guidelines and containment procedures.
 Emergency Preparedness:
 Postexposure Plan: Develop a comprehensive plan for incident response.
 Swift Action: Ensure prompt medical evaluation and treatment.
 Overall Goal:
 Establish a secure lab environment through vigilance, proactive measures, and
rapid response to incidents.