MB 558: Medically Important Viruses

2.1 Poxviruses

Smallpox Virus

Introduction

Smallpox was a severe contagious disease caused by variola virus. Historically, smallpox produced characteristic fever followed by a generalized vesiculopustular rash. Variola virus belongs to the genus Orthopoxvirus within the family Poxviridae.

Smallpox was one of the most important viral diseases in human history. Following an extensive global eradication programme based on surveillance, case detection, isolation and vaccination, naturally occurring smallpox was eradicated. The last naturally occurring case was reported in 1977 and the World Health Organization declared smallpox eradicated in 1980.

Taxonomic classification

Morphology and structure

Poxviruses are unusually large and structurally complex. Mature virions are often described as brick-shaped or oval. Unlike many enveloped viruses, their particles contain a complex internal structure consisting of a central nucleoprotein core and lateral bodies.

Genome

Variola virus contains a large linear double-stranded DNA genome. The genome contains genes required for viral replication, transcription, structural protein synthesis, immune evasion and interaction with the host cell.

A remarkable feature of poxviruses is that they encode many of their own enzymes required for transcription and DNA replication, allowing replication to occur in the cytoplasm rather than depending entirely on the host-cell nucleus.

Physiology and biological properties

• Large and complex DNA virus.
• Replication occurs in the cytoplasm.
• Produces characteristic cytoplasmic inclusion bodies.
• Possesses multiple structural proteins and viral enzymes.
• Relatively resistant to environmental conditions compared with many other enveloped viruses.

Replication cycle

Poxvirus replication is unusual because the virus carries or encodes much of the enzymatic machinery required for transcription and genome replication. Replication takes place in the cytoplasm of infected cells.

Transmission

• Primarily by respiratory droplets and aerosols during close contact.
• Direct contact with lesions and infectious material.
• Contact with contaminated materials can contribute to transmission.

Pathogenesis

Following entry through the respiratory tract, the virus replicates in local lymphoid tissues and subsequently spreads through the bloodstream. Primary viremia is followed by further multiplication in reticuloendothelial tissues. A secondary viremia is associated with widespread dissemination and the appearance of characteristic skin lesions.

The extensive skin and mucosal involvement results from viral replication within epithelial tissues. Host inflammatory and immune responses contribute to tissue injury and systemic manifestations.

Clinical manifestations

• Incubation period followed by an acute febrile illness.
• Severe headache, backache and malaise.
• Characteristic generalized rash.
• Lesions progress through macule → papule → vesicle → pustule → crust.
• Lesions in a given anatomical area tend to be at a similar stage.
• Scarring may occur following healing.

Complications

• Secondary bacterial infection.
• Severe dehydration.
• Encephalitis.
• Hemorrhagic forms.
• Extensive scarring.
• Death in severe disease.

Laboratory diagnosis

Because smallpox has been eradicated as a naturally occurring disease, diagnosis of a suspected case is a highly specialized public-health and biosafety procedure. Routine laboratory handling of suspected variola virus is not appropriate.

Specimen

• Lesion material from appropriate stages of disease.
• Vesicular or pustular material.
• Crust material where appropriate.

Direct detection

Characteristic viral particles may be demonstrated using electron microscopy in specialized settings, although morphology alone cannot reliably distinguish all orthopoxviruses.

Molecular diagnosis

Nucleic-acid amplification assays are important for detection and characterization of orthopoxvirus DNA. Confirmatory testing requires specialized reference laboratories.

Serology

Serological methods may demonstrate an immune response but are generally less useful than direct molecular detection for immediate confirmation.

Treatment

Because naturally occurring smallpox has been eradicated, routine clinical treatment is not part of ordinary diagnostic practice. In the event of a suspected case, specialized public-health and infectious-disease protocols would guide management.

Prevention and control

• Rapid identification and notification of suspected cases.
• Isolation and infection-control measures.
• Contact tracing.
• Vaccination strategies according to public-health protocols.
• Surveillance.
• Strict laboratory biosafety.

2.2 Herpesviruses

General structure of herpesviruses

Herpesvirus particles consist of a linear dsDNA genome enclosed within an icosahedral capsid. The capsid is surrounded by a proteinaceous tegument and an outer lipid envelope containing viral glycoprotein spikes.

General herpesvirus replication

Herpesvirus replication begins with attachment of viral glycoproteins to specific cellular receptors. Fusion of the viral envelope with the cell membrane permits entry of the nucleocapsid and tegument. The capsid is transported toward the nucleus where viral DNA is released.

Immediate-early proteins regulate the infection, early proteins participate in viral DNA synthesis, and late proteins mainly form structural components. New capsids assemble in the nucleus. Virions acquire tegument and envelope during maturation and are released through cellular membranes.

Important herpesviruses in the syllabus

2.2.1 Herpes Simplex Virus

Introduction

Herpes simplex viruses are enveloped dsDNA viruses belonging to the genus Simplexvirus. HSV-1 is classically associated with orolabial infection, while HSV-2 is strongly associated with genital infection, although both viruses can infect either anatomical site.

Genome and important proteins

HSV possesses a large linear dsDNA genome encoding numerous structural, regulatory and replication-associated proteins. Important viral glycoproteins include gB, gC, gD, gH and gL, which participate in attachment, receptor recognition and membrane fusion.

Transmission

• Direct contact with infected secretions.
• Saliva and oral secretions.
• Sexual contact.
• Perinatal transmission during delivery.

Pathogenesis

HSV initially replicates in epithelial cells at the portal of entry and produces vesicular lesions. The virus then enters sensory nerve endings and travels by retrograde axonal transport to sensory ganglia where it establishes latency.

Reactivation may occur following stress, fever, ultraviolet exposure, immunosuppression or other triggers. Reactivated virus travels along sensory nerves to the skin or mucosa and produces recurrent lesions.

Clinical manifestations

• Primary gingivostomatitis.
• Herpes labialis.
• Genital herpes.
• Herpetic keratitis.
• Herpetic whitlow.
• Herpes encephalitis.
• Neonatal herpes.

Laboratory diagnosis

Laboratory diagnosis depends on the site and stage of infection. Molecular detection is particularly important because it is sensitive and rapid.

Specimens

• Vesicle or lesion swab.
• Genital lesion material.
• CSF in suspected encephalitis.
• Neonatal specimens where indicated.

Molecular diagnosis

PCR or real-time PCR can detect HSV DNA in lesion material or CSF. PCR of CSF is particularly important in suspected HSV encephalitis.

Antigen detection

Direct fluorescent antibody and other antigen-detection methods may be used in selected settings.

Culture

HSV can be isolated in susceptible cell cultures, where characteristic cytopathic effects may develop.

Serology

Type-specific antibody testing can support diagnosis in selected situations, although serology is generally less useful than direct detection for localized active lesions.

Treatment

Acyclovir and related nucleoside analogues are important antiviral agents used for HSV infections. Severe disease may require intravenous therapy. Treatment choice depends on the site, severity and host condition.

Prevention

• Avoid direct contact with active lesions.
• Safe sexual practices reduce transmission risk.
• Pregnancy requires special management when genital HSV is present.
• Appropriate antiviral management can reduce recurrence and transmission risk.

2.2.2 Varicella-Zoster Virus

Introduction

Varicella-zoster virus (VZV), also known as human alphaherpesvirus 3, causes two major clinical conditions: primary varicella (chickenpox) and reactivation as herpes zoster (shingles).

Transmission

• Respiratory droplets and aerosols.
• Direct contact with vesicular fluid.

Pathogenesis

Primary infection occurs through the respiratory tract followed by replication in lymphoid tissues and viremia. The virus disseminates to the skin, producing the characteristic varicella rash. Following primary infection, VZV becomes latent in sensory ganglia. Reactivation later in life results in herpes zoster.

Clinical manifestations

• Fever and malaise.
• Generalized pruritic vesicular rash.
• Lesions appearing in crops.
• Herpes zoster with painful dermatomal vesicles.

Complications

• Secondary bacterial infection.
• Pneumonia.
• Cerebellitis.
• Encephalitis.
• Severe disease in immunocompromised individuals.
• Congenital and neonatal disease.

Laboratory diagnosis

PCR from vesicular lesion material is a highly useful diagnostic method. Viral DNA can also be detected from appropriate specimens in complicated disease.

Serology

VZV-specific IgM may support recent infection, while IgG is useful for determining immune status and evidence of previous exposure.

Prevention

Vaccination is the major preventive strategy against varicella and zoster. Post-exposure management may be considered for selected high-risk individuals.

2.2.3 Cytomegalovirus

Introduction

Cytomegalovirus (CMV) is a betaherpesvirus capable of establishing lifelong persistent infection. In healthy individuals infection is often asymptomatic or produces a mononucleosis-like illness, whereas severe disease can occur in fetuses, newborns and immunocompromised patients.

Transmission

• Saliva.
• Urine.
• Sexual contact.
• Blood and blood products.
• Organ transplantation.
• Transplacental transmission.
• Breast milk.

Pathogenesis

CMV infects epithelial and other cell types and establishes persistent infection. Reactivation or primary infection in immunocompromised patients may produce severe tissue-invasive disease.

Clinical manifestations

• Asymptomatic infection.
• Mononucleosis-like illness.
• Retinitis.
• Pneumonitis.
• Colitis.
• Esophagitis.
• Encephalitis.
• Congenital CMV disease.

Congenital CMV

Congenital infection may result in growth restriction, jaundice, hepatosplenomegaly, microcephaly, hearing impairment and neurological abnormalities.

Laboratory diagnosis

• PCR/real-time PCR for CMV DNA.
• Antigen detection assays in selected settings.
• Serology for specific clinical questions.
• Histopathology showing characteristic inclusion bodies.
• Virus culture in specialized laboratories.

Treatment

Ganciclovir, valganciclovir and other antiviral agents may be used in selected patients with significant CMV disease.

2.2.4 Human Herpesvirus 6

HHV-6 is a betaherpesvirus acquired commonly during childhood. It is strongly associated with roseola infantum and can establish persistent infection.

Clinical importance

• Roseola infantum.
• High fever followed by rash.
• Febrile seizures in some children.
• Encephalitis in selected immunocompromised patients.
• Reactivation after transplantation.

Laboratory diagnosis

Molecular detection by PCR is commonly used when active HHV-6 disease is suspected. Interpretation requires caution because viral DNA may persist in the host.

2.2.5 Human Herpesvirus 7

HHV-7 is another betaherpesvirus that establishes persistent infection and is closely related biologically to HHV-6.

Clinical importance

• Primary childhood infection.
• Roseola-like illness in some cases.
• Persistent infection.
• Possible reactivation in immunocompromised patients.

Laboratory diagnosis

PCR-based detection may be used in selected clinical situations. Because viral DNA may persist, detection must be interpreted together with clinical findings.

2.2.6 Epstein-Barr Virus

Introduction

Epstein-Barr virus (EBV) is a gammaherpesvirus with a strong tropism for B lymphocytes and epithelial cells. It is best known as the major cause of infectious mononucleosis and is associated with several lymphoid and epithelial malignancies.

Transmission

EBV is primarily transmitted through saliva. Infection may occur through close personal contact.

Pathogenesis

EBV infects epithelial cells and B lymphocytes. Viral proteins promote B-cell activation and proliferation. The host immune response, particularly cytotoxic T-cell activity, contributes substantially to the clinical features of infectious mononucleosis.

Clinical manifestations

• Fever.
• Pharyngitis.
• Lymphadenopathy.
• Fatigue.
• Hepatosplenomegaly.

Associated malignancies

• Burkitt lymphoma.
• Hodgkin lymphoma in selected settings.
• Nasopharyngeal carcinoma.
• Post-transplant lymphoproliferative disorders.

Laboratory diagnosis

Heterophile antibody test

Heterophile antibody testing can support the diagnosis of infectious mononucleosis, particularly in appropriate age groups and clinical settings.

Specific EBV serology

Molecular diagnosis

EBV DNA can be detected and quantified by PCR, especially in selected immunocompromised patients and lymphoproliferative disorders.

2.3 Picornaviruses

Important medically relevant picornaviruses

• Poliovirus.
• Coxsackieviruses.
• Echoviruses.
• Rhinoviruses.
• Hepatitis A virus.

General structure

Genome

Picornaviruses contain a positive-sense single-stranded RNA genome that can function as messenger RNA after entry into the host cell. The genome contains a single large open reading frame encoding a polyprotein that is processed into structural and non-structural proteins.

Replication

After attachment and entry, the viral RNA is released into the cytoplasm. Because it is positive-sense RNA, it can be translated directly by host ribosomes. Viral proteins are synthesized as a polyprotein and subsequently cleaved into functional proteins.

Viral RNA replication occurs through a complementary negative-sense RNA intermediate. New positive-sense genomes are synthesized and packaged into capsids.

Poliovirus

Poliovirus is an enterovirus that primarily infects the gastrointestinal tract but may invade the central nervous system and cause acute flaccid paralysis. Transmission is mainly fecal-oral.

Clinical manifestations

• Asymptomatic infection.
• Minor febrile illness.
• Aseptic meningitis.
• Paralytic poliomyelitis.

Laboratory diagnosis

• Stool specimen is particularly important.
• RT-PCR can detect poliovirus RNA.
• Virus isolation may be performed in specialized laboratories.
• Serological methods have limited value for routine acute diagnosis.

Prevention

Vaccination is the major preventive measure. High vaccination coverage, surveillance and rapid investigation of suspected acute flaccid paralysis are essential components of polio control.

Coxsackieviruses and Echoviruses

These enteroviruses are associated with a broad spectrum of disease including aseptic meningitis, hand-foot-and-mouth disease, herpangina, myocarditis, pericarditis and respiratory or febrile illnesses.

Laboratory diagnosis

RT-PCR from appropriate clinical specimens is widely used. CSF is particularly important when central nervous system disease is suspected.

Rhinoviruses

Rhinoviruses are major causes of the common cold. They primarily infect the upper respiratory tract.

Laboratory diagnosis

Diagnosis is usually clinical. Molecular assays can detect rhinovirus RNA when laboratory confirmation is required.

Hepatitis A Virus

HAV causes acute hepatitis and is transmitted mainly by the fecal-oral route. Unlike hepatitis B and C, it does not normally cause chronic infection.

Laboratory diagnosis

• Anti-HAV IgM indicates recent/acute infection.
• Anti-HAV IgG indicates past infection or immunity.
• HAV RNA detection is used in specialized molecular applications.

2.4 Orthomyxovirus — Influenza Virus

Introduction

Influenza viruses are enveloped, segmented, negative-sense single-stranded RNA viruses belonging to the family Orthomyxoviridae. Influenza A and B are major causes of seasonal human influenza, while influenza A viruses also infect many animal species and have pandemic potential.

Structure

Genome

Influenza A and B viruses contain eight segments of negative-sense RNA. Genome segmentation allows reassortment when two compatible influenza viruses infect the same cell.

Important proteins

Replication

After attachment through HA, the virus enters the cell by endocytosis. Acidification of the endosome triggers conformational changes and membrane fusion. The viral ribonucleoprotein complexes are transported into the nucleus. Influenza is unusual among RNA viruses because transcription and replication of its genome occur in the nucleus.

Viral mRNAs are produced, viral proteins are synthesized and new genomic RNA segments are generated. Assembly occurs at the plasma membrane and new virions bud from the cell surface.

Antigenic variation

Antigenic drift

Antigenic drift results from gradual accumulation of mutations, especially in genes encoding surface antigens. It contributes to seasonal epidemics and is one reason influenza vaccines require periodic updating.

Antigenic shift

Antigenic shift is a major change associated with reassortment of segmented influenza A genomes. It can produce a novel combination of surface antigens against which population immunity may be limited.

Clinical manifestations

• Sudden fever.
• Headache.
• Myalgia.
• Malaise.
• Dry cough.
• Sore throat.
• Upper and lower respiratory disease.

Complications

• Viral pneumonia.
• Secondary bacterial pneumonia.
• Otitis media.
• Exacerbation of chronic respiratory disease.
• Severe systemic disease in high-risk patients.

Laboratory diagnosis

Specimens

• Nasopharyngeal swab.
• Nasal or throat specimens.
• Lower respiratory specimens in severe disease.

Molecular diagnosis

RT-PCR and real-time RT-PCR are widely used for detection and characterization of influenza RNA.

Antigen detection

Rapid antigen detection tests can provide quick results but generally have lower sensitivity than molecular assays.

Virus isolation

Influenza can be isolated in appropriate cell culture or embryonated eggs in specialized laboratories.

Serology

Paired sera may be used for epidemiological or retrospective diagnosis, although serology is not generally the preferred method for acute routine diagnosis.

Prevention

• Seasonal vaccination.
• Respiratory hygiene.
• Hand hygiene.
• Appropriate infection-control measures.
• Antiviral treatment or prophylaxis in selected situations.

2.5 Paramyxoviruses

The syllabus includes measles virus, mumps virus, human parainfluenza viruses and respiratory syncytial virus. These viruses are enveloped negative-sense RNA viruses. Their exact modern family placement differs for some members; for examination purposes, the syllabus grouping should be retained while using current scientific terminology where appropriate.

General structure

2.5.1 Measles Virus

Introduction

Measles virus causes an acute highly contagious systemic infection characterized by fever, cough, coryza, conjunctivitis and a generalized maculopapular rash.

Transmission

Transmission occurs predominantly through respiratory droplets and airborne spread in susceptible populations.

Pathogenesis

The virus initially infects respiratory epithelial cells and local immune cells. It spreads through lymphoid tissues and produces viremia. Dissemination to multiple organs results in the characteristic systemic disease.

Clinical features

• High fever.
• Cough.
• Coryza.
• Conjunctivitis.
• Koplik spots.
• Generalized maculopapular rash.

Complications

• Otitis media.
• Pneumonia.
• Diarrhea.
• Encephalitis.
• Subacute sclerosing panencephalitis.

Laboratory diagnosis

• Measles-specific IgM.
• Seroconversion or significant change in IgG.
• RT-PCR for viral RNA in appropriate specimens.
• Viral isolation in specialized laboratories.

Prevention

Measles-containing vaccination is the major preventive strategy. High vaccination coverage is essential for elimination and outbreak control.

2.5.2 Mumps Virus

Introduction

Mumps virus causes an acute systemic infection with characteristic swelling of the salivary glands, especially the parotid glands.

Transmission

Transmission occurs through respiratory droplets, saliva and close contact.

Clinical manifestations

• Fever.
• Headache.
• Parotitis.
• Orchitis.
• Oophoritis.
• Meningitis.
• Encephalitis.
• Pancreatitis.

Laboratory diagnosis

• RT-PCR from buccal/oral specimens.
• Mumps-specific IgM.
• Seroconversion or rise in IgG in selected cases.

Prevention

Vaccination is the main preventive measure.

2.5.3 Human Parainfluenza Viruses

Human parainfluenza viruses are important causes of respiratory disease, particularly in infants and young children. Different types are associated with different clinical syndromes.

Clinical manifestations

• Common cold-like illness.
• Croup.
• Bronchiolitis.
• Bronchitis.
• Pneumonia.

Laboratory diagnosis

• RT-PCR.
• Multiplex respiratory viral panels.
• Antigen detection in selected settings.
• Virus culture in specialized laboratories.

2.5.4 Human Respiratory Syncytial Virus

Respiratory syncytial virus is a major cause of lower respiratory tract disease in infants and young children and can also produce significant illness in older adults and immunocompromised patients.

Important structural feature

RSV has a fusion protein that promotes fusion of infected cells, producing multinucleated giant cells known as syncytia.

Clinical manifestations

• Upper respiratory infection.
• Bronchiolitis.
• Pneumonia.
• Apnea in young infants.
• Severe respiratory disease in high-risk individuals.

Laboratory diagnosis

• RT-PCR.
• Rapid antigen detection.
• Immunofluorescence.
• Virus culture in selected laboratories.

2.6 Arboviruses

General transmission cycle

2.6.1 Dengue Virus

Introduction

Dengue virus is an enveloped positive-sense RNA virus transmitted primarily by Aedes mosquitoes. Dengue infection ranges from an asymptomatic or mild febrile illness to severe dengue with plasma leakage, bleeding and shock.

Structure

Transmission

Dengue is mainly transmitted by infected female Aedes mosquitoes, especially Aedes aegypti. The mosquito acquires virus during a blood meal and later transmits it during subsequent feeding.

Clinical manifestations

• High fever.
• Severe headache.
• Retro-orbital pain.
• Myalgia and arthralgia.
• Rash.
• Nausea and vomiting.

Severe dengue

• Plasma leakage.
• Hemoconcentration.
• Bleeding.
• Thrombocytopenia.
• Shock.
• Organ impairment.

Laboratory diagnosis

Early infection

• NS1 antigen detection.
• RT-PCR for dengue RNA.

Later phase

• Dengue-specific IgM.
• IgG serology.

The interpretation of dengue serology depends strongly on the timing of specimen collection and whether the patient is experiencing a primary or secondary infection.

Prevention

• Vector control.
• Removal of mosquito breeding sites.
• Personal protection against mosquito bites.
• Appropriate vaccination according to local recommendations and eligibility.

2.6.2 Japanese Encephalitis Virus

Japanese encephalitis virus is a mosquito-borne flavivirus and an important cause of viral encephalitis in parts of Asia.

Transmission cycle

The virus is maintained in an enzootic cycle involving mosquitoes and vertebrate amplifying hosts, particularly pigs and water birds. Humans are generally incidental dead-end hosts.

Clinical manifestations

• Fever.
• Headache.
• Altered consciousness.
• Seizures.
• Neurological deficits.
• Encephalitis.

Laboratory diagnosis

Detection of virus-specific IgM in CSF or serum is an important diagnostic method. Molecular detection may be useful in selected settings, although viral RNA may be transient in clinical specimens.

Prevention

• Vaccination.
• Mosquito control.
• Personal protection from mosquito bites.

2.6.3 Yellow Fever Virus

Yellow fever virus is a flavivirus transmitted by mosquitoes. It causes a systemic febrile illness ranging from mild infection to severe hemorrhagic and hepatic disease.

Clinical manifestations

• Fever.
• Headache.
• Myalgia.
• Nausea and vomiting.
• Jaundice.
• Hemorrhagic manifestations.
• Hepatic failure in severe disease.

Laboratory diagnosis

• RT-PCR during appropriate early stages.
• Serological detection of specific antibodies.
• Specialized reference testing may be required because of cross-reactivity among flaviviruses.

Prevention

An effective vaccine is available. Mosquito control and prevention of mosquito exposure are also important.

2.7 Retroviruses

General structure

Replication

The defining feature of retroviral replication is reverse transcription. After entry and uncoating, viral RNA is converted into DNA by reverse transcriptase. The resulting double-stranded viral DNA enters the nucleus and integrates into the host genome with the help of integrase.

The integrated provirus is transcribed by host cellular machinery. Viral RNA serves as both genomic RNA and messenger RNA. Viral proteins are synthesized, virions assemble at the plasma membrane and budding releases immature particles. Viral protease processes precursor proteins to produce mature infectious virions.

2.7.1 Human Immunodeficiency Virus

Introduction

Human immunodeficiency virus (HIV) is a retrovirus that primarily infects CD4-positive T lymphocytes and other susceptible cells. Progressive destruction or dysfunction of the immune system can result in acquired immunodeficiency syndrome (AIDS).

Types

• HIV-1 — globally predominant.
• HIV-2 — concentrated mainly in West Africa but also found elsewhere.

Important viral proteins

Target cells

• CD4 T lymphocytes.
• Macrophages.
• Dendritic cells.

Transmission

• Sexual transmission.
• Blood and contaminated needles.
• Mother-to-child transmission.
• Transfusion of infected blood or blood products when not appropriately screened.

Pathogenesis

HIV enters susceptible cells through interaction between gp120 and the CD4 receptor together with a chemokine co-receptor. Viral fusion permits entry and reverse transcription. Viral DNA integrates into the host genome and establishes a provirus.

Progressive loss and dysfunction of CD4 T lymphocytes impair cell-mediated immunity. As immunodeficiency progresses, patients become susceptible to opportunistic infections, certain malignancies and other complications.

Stages of infection

1. Acute HIV infection: may resemble a febrile mononucleosis-like illness.
2. Clinical latency/chronic infection: virus persists and immune damage progresses over time.
3. Advanced HIV infection/AIDS: severe immunodeficiency with opportunistic infections and selected malignancies.

Clinical manifestations

• Fever.
• Generalized lymphadenopathy.
• Weight loss.
• Recurrent infections.
• Oral candidiasis.
• Opportunistic infections.
• Selected malignancies.

Laboratory diagnosis of HIV

1. Antibody/antigen screening

Modern laboratory algorithms commonly use highly sensitive assays that detect HIV antibodies, HIV antigen or both. Fourth-generation assays detect p24 antigen together with antibodies and can identify infection earlier than antibody-only tests.

2. Confirmatory testing

Reactive screening results require testing according to the validated diagnostic algorithm of the laboratory or national programme. Modern algorithms use supplemental antibody differentiation and/or nucleic-acid testing rather than relying on older Western blot algorithms.

3. Nucleic-acid testing

HIV RNA can be detected by nucleic-acid amplification methods. NAT is useful in early infection and in selected diagnostic situations.

4. Viral load

Quantitative HIV RNA testing is used primarily for monitoring response to antiretroviral therapy and assessing virological suppression.

5. CD4 count

CD4 T-cell count provides information about immune status and helps assess the risk of opportunistic disease.

Treatment

HIV infection is treated with combination antiretroviral therapy (ART). Modern treatment uses combinations of drugs acting at different stages of the viral life cycle. Effective therapy can suppress viral replication, restore or preserve immune function and substantially reduce morbidity and mortality.

Prevention

• Condom use and safer sexual practices.
• Screening of donated blood.
• Use of sterile injection equipment.
• Pre-exposure prophylaxis in appropriate individuals.
• Post-exposure prophylaxis when indicated.
• Testing and treatment during pregnancy.
• Prevention of mother-to-child transmission.

2.7.2 Human T-Lymphotropic Virus

Introduction

Human T-lymphotropic viruses are deltaretroviruses. HTLV-1 is the major medically important member and is associated with adult T-cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis.

Transmission

• Breastfeeding.
• Sexual transmission.
• Blood transfusion.
• Contaminated needles.

Pathogenesis

HTLV-1 infects T lymphocytes and integrates its DNA into the host genome. The viral regulatory protein Tax has important effects on cellular transcription and proliferation. Persistent infection may contribute to malignant transformation or inflammatory neurological disease in a small proportion of infected individuals.

Clinical manifestations

• Adult T-cell leukemia/lymphoma.
• HTLV-1-associated myelopathy.
• Tropical spastic paraparesis.
• Other inflammatory complications in selected patients.

Laboratory diagnosis

Serology

Screening tests detect antibodies against HTLV antigens. Reactive specimens require confirmatory testing according to the laboratory algorithm.

Western blot / immunoblot

Immunoblot methods may help confirm infection and differentiate HTLV reactivity according to validated criteria.

Molecular diagnosis

PCR can detect proviral DNA in infected cells and can be useful when serological results require clarification or when proviral characterization is required.

Prevention

• Screening of donated blood.
• Safer sexual practices.
• Avoidance of sharing contaminated needles.
• Appropriate management of breastfeeding in infected mothers according to local recommendations.

2.8 Major Comparison Tables

DNA versus RNA viruses in this syllabus

Important diagnostic methods

2.9 Important Examination Questions