Viral Infections

Serologic and Molecular Detection of Infectious Diseases

Viral Infections

  • Categories of viral infections include:

    • Viral Hepatitis

    • HIV

    • Dengue

    • Herpes virus infections:

      • Infectious Mononucleosis

      • Epstein Barr Virus

      • Cytomegalovirus

Viral Hepatitis

Overview of Hepatitis Viruses

  • HAV (Hepatitis A Virus)

    • Type/Family: Picornaviridae, ssRNA

    • Incubation Period: 15-45 days

    • Transmission: Fecal-oral

    • Chronic Progression: No

    • Clinical Significance: Acute, self-limiting

  • HBV (Hepatitis B Virus)

    • Type/Family: Hepadnaviridae, dsDNA

    • Incubation Period: 45-160 days

    • Transmission: Sex, blood transfusion, sharing of needles, transplacental

    • Chronic Progression: Yes

    • Clinical Significance: Acute or chronic (10-90%); risk for cirrhosis and cancer, spontaneous resolution in 15-20% of cases.

  • HCV (Hepatitis C Virus)

    • Type/Family: Flaviviridae, ssRNA

    • Incubation Period: 15-150 days

    • Transmission: Same as HBV

    • Chronic Progression: Yes

    • Clinical Significance: 80-85% will have chronic disease.

  • HDV (Hepatitis D Virus)

    • Type/Family: Delta virus, requires HBV for replication

    • Incubation Period: 30-60 days

    • Transmission: Same as HBV

    • Chronic Progression: Yes

    • Clinical Significance: Superinfection/confection with HBV; acute self-limiting in certain cases.

  • HEV (Hepatitis E Virus)

    • Type/Family: Caliciviridae, ssRNA

    • Incubation Period: 15-60 days

    • Transmission: Fecal-oral

    • Chronic Progression: No

    • Clinical Significance: Fulminant liver failure in pregnant women.

Important Serological Markers

  • HAV:

    • HAV RNA: Present in stool and plasma for ~18 days after clinical onset.

    • Anti-HAV IgM: Indicates recent infection, develops 2-3 weeks after exposure, persists for 3-6 months.

    • Anti-HAV IgG: Develops 1-2 weeks after IgM, provides lifelong immunity.

  • HBV:

    • HBsAg: Marker of acute infection and infectivity.

    • HBeAg: Indicates active infection with increased infectivity risk.

    • Anti-HBc IgM: Indicates current or recent infection.

    • Total Anti-HBc: Shows current or past infection.

    • Anti-HBe: Recovery marker.

    • Anti-HBs: Immunity marker.

    • HBV DNA: Used for monitoring therapy.

  • HCV:

    • Anti-HCV: Used to diagnose Hepatitis C infection (detectable ~4 weeks post-infection).

    • HCV-RNA: Monitors response to antiviral therapy and aids acute diagnosis.

Clinical Relevance of HBV Serology

  • Markers in Time Course:

    • Early infection: HBsAg positive, Anti-Hbs negative, Anti-HBc IgM positive, etc.

    • Window period: HBsAg negative, Anti-HBs negative, etc.

    • Chronic infection: HBsAg positive, Anti-HBc negative, etc.

HIV

Overview

  • Genus: Lentivirinae

  • Family: Retroviridae

  • Type: ssRNA

  • Size: 100 nm in diameter

  • Modes of Transmission:

    • Sexual contact

    • Blood transfusion

    • Needle sharing (drug use)

    • Transplantation

    • Transplacental and breastfeeding.

Important Proteins and Enzymes

  • Gp41/Gp120 complex: Key receptor for host CD4 interaction.

  • p24: Nucleocapsid core protein.

  • Enzymes:

    • Reverse Transcriptase: Converts viral RNA to DNA.

    • Integrase: Inserts viral DNA into host DNA.

    • Protease: Cleaves proteins for virion assembly.

Clinical Significance

  • Stages:

    • Primary Stage: Often asymptomatic initially; flu-like symptoms.

    • Intermediate Stage: Symptoms include lymphadenopathy, fever, weight loss, etc.

    • Final Stage: AIDS marked by T4 cells <200/mm², leads to opportunistic infections.

Dengue

Overview

  • Type: Envelope RNA virus

  • Family: Flaviviridae

  • Serotypes: DENV-1, DENV-2, DENV-3, DENV-4

  • Vector: Aedes aegypti.

Diagnostic Tests

  • Viral Isolation: Gold standard; takes 6-10 days.

  • RT-PCR: Detects dengue genomic RNA.

  • NS1 Test: Detects NS1 glycoprotein during acute infection.

  • IgM-capture ELISA: First detectable IgM appears 4-5 days after infection.

Epstein Barr Virus (EBV)

Overview

  • Type: Double-stranded DNA virus

  • Family: Herpesviridae

  • Modes of Transmission: Saliva, blood transfusion, transplacental.

Associated Diseases

  1. Infectious Mononucleosis (IM): Symptoms include fever, malaise, lymphadenopathy.

  2. Other Diseases: Linked to Burkitt’s lymphoma and nasopharyngeal carcinoma.

Immunologic Features

  1. Target Cells: Primarily B cells.

  2. Hallmark: Presence of Downey cells (atypical lymphocytes).

Serologic Tests

  1. Most specific: EBV DNA PCR.

  2. Heterophile Antibody Tests (e.g., Monospot Test).

C-Reactive Protein (CRP)

Overview

  • A protein indicating acute inflammation and various infections.

  • Properties: Synthesized in liver, sensitive but nonspecific.

Diagnostic Use

  • CRP assays provide sensitivity compared to ESR and WBC count.

  • Rapid Slide Test: Detects CRP via agglutination reactions.

Conclusion

  • Understanding serological and molecular detection methods is crucial for diagnosing viral infections such as Hepatitis, HIV, Dengue, and EBV.