Clinical Infectious Diseases Review for Boards

Overview

This lecture reviews selected infectious diseases that frequently appear in primary care and on board exams. It focuses on:

• HIV and AIDS.
• Tick-borne illnesses: Lyme disease and Rocky Mountain spotted fever.
• Influenza.
• Tuberculosis.

For each, it covers key concepts, screening and diagnosis, core clinical features, prevention strategies (including vaccines and PrEP), and foundational management principles.

HIV and AIDS

Core Concepts

• HIV is a virus that progressively impairs the immune system and is the underlying cause of AIDS.
• AIDS is the most advanced stage of HIV infection and is defined by severe immunosuppression and/or certain associated conditions.

Definition of AIDS

AIDS is diagnosed when:

• CD4 count < 200 cells/mm³
  OR
• Laboratory documentation of HIV infection plus at least one of:
  • Broad-spectrum opportunistic infections.
  • Certain malignant neoplasms.
  • Specific nonspecific syndromes (e.g., AIDS dementia, AIDS wasting).

These opportunistic diseases arise because the immune system is too weak to control them.

Transmission of HIV

• Sexual:
  • Vaginal, anal, or oral sex with infected partner.
• Parenteral:
  • IV drug use (needle sharing).
  • Other contaminated needle or blood exposures.
• Vertical:
  • From mother to child during pregnancy or delivery.

Pathophysiology

• HIV targets CD4 T cells.
  • Must bind to CD4 and one of two chemokine receptors to enter cells.
• As CD4 T cell counts decline:
  • Immune system capacity drops.
  • Susceptibility to opportunistic infections and malignancies increases.
• CD4 count is a major marker of immune function and disease stage.

Natural History Without Antiretroviral Therapy (ART)

• Approximate course (without ART):
  • ~8 years from initial HIV infection to first AIDS-defining complication.
  • ~1 year from first complication to death.
• With appropriate ART:
  • Patients can live long, relatively healthy lives with near-normal daily functioning.

HIV Screening and Risk Assessment

Routine Screening Recommendations

• CDC:
  • Offer HIV testing at least once to all persons 13–64 years, regardless of perceived risk.
• USPSTF:
  • Recommends screening for ages 15–65 years (similar overall range).

Who Needs More Frequent Testing?

High-risk patients should be tested at least annually. Examples:

• People who trade sexual acts for money or drugs.
• People whose sexual partners are known to have HIV.
• Men who have sex with men (MSM).
• Heterosexual persons with more than one partner since last HIV screen.
• Individuals with other behaviors that significantly increase HIV exposure risk (e.g., inconsistent condom use plus multiple partners, injection drug use).

HIV Infection Stages and Clinical Presentation

Primary HIV Infection and Window Period

• Primary HIV infection:
  • HIV is present in the blood.
  • Standard serologic antibody tests may still be negative.
• Window period:
  • Time from infection until antibodies become detectable.
  • Lasts several weeks up to ~3 months.
  • During this period, a person can have HIV and a negative antibody test.

Seroconversion Illness

• Occurs as the immune system begins producing antibodies.
• Appears like a nonspecific viral illness:
  • Fever.
  • Muscle aches.
  • Headaches.
  • Rash.
• May not be recognized as HIV-related at the time.

Asymptomatic Phase

• After primary infection and seroconversion:
  • Patients are often asymptomatic for years.
  • They may be completely unaware of their infection.
• No obvious signs or symptoms to reliably distinguish them clinically.

Clinical Syndromes Between Primary Infection and AIDS

As CD4 count gradually declines, various conditions may arise before formal AIDS:

• Malignant neoplasms:
  • Cervical carcinoma.
  • Anal carcinoma.
  • Lymphomas.
• Infections and inflammatory conditions:
  • Tuberculosis (can occur at relatively higher CD4 counts).
  • Shingles (herpes zoster).
  • Psoriasis.
  • Severe pneumonia.
  • Other opportunistic-type infections.

CD4 Count and Opportunistic Conditions

As CD4 count drops, specific complications become more likely:

• CD4 < 200 is a key marker of profound immunosuppression and AIDS.
• CD4 < 50 represents extremely severe immune compromise.

Physical Examination in HIV/AIDS

When examining a patient with known or suspected HIV:

• Neurologic:
  • Perform a careful neuro exam.
  • Look for focal deficits (weakness, asymmetry) and cognitive changes (confusion, memory issues) that might suggest CNS involvement, dementia, or opportunistic CNS infection.
• Skin:
  • Inspect for Kaposi sarcoma lesions (violaceous, red-purple patches or nodules).
• Oral cavity:
  • Look for thrush (oral candidiasis).
  • Check for oral Kaposi sarcoma lesions.
• Abdomen:
  • Assess liver for enlargement or tenderness.
• Genital exam:
  • Evaluate for coexisting sexually transmitted infections (STIs).
• Eyes:
  • If CD4 < 100:
    • Include a formal retinal exam to evaluate for CMV retinitis.

HIV Testing

Serologic Antibody Tests

• Detect antibodies to HIV-1 and HIV-2.
• Antibody development:
  • May take 3 weeks to 3 months to reach detectable levels.
• Implications:
  • A person tested within the first 3 months after exposure:
    • Could have a false-negative test.
    • Should be retested after 3 months to confirm negative status.
• Rapid HIV tests:
  • Fall into this antibody category.
  • Provide quick results but share the same window period limitation.

Virologic / Antigen Tests

• Detect HIV antigens (such as the p24 antigen).
• Current CDC recommendation:
  • Use combination antigen/antibody testing (4th-generation tests) to improve early detection.

CDC HIV Testing Algorithm (Simplified)

1. Initial test:
   • HIV-1/HIV-2 antigen/antibody combination assay.
2. If negative for HIV-1, HIV-2, and p24 antigen:
   • Result: HIV negative.
3. If positive:
   • Could represent:
     • HIV-1 infection.
     • HIV-2 infection.
     • Both.
     • Or an indeterminate result.
4. If indeterminate:
   • Perform nucleic acid test (NAT) for further clarification.
   • Historically, the Western blot was used for confirmatory testing; NAT is now emphasized for definitive diagnosis of HIV-1 infection.

HIV Pre-Exposure Prophylaxis (PrEP)

Purpose and Role in Primary Care

• PrEP is used to prevent HIV infection in individuals at high risk.
• Primary care providers:
  • Should routinely assess risk behaviors.
  • Offer education and PrEP options when appropriate.

Who Might Benefit?

• High-risk behaviors include:
  • Sexual intercourse with multiple partners.
  • Inconsistent condom use.
  • Injection drug use with shared equipment.
  • Ongoing exposure through partners known or likely to have HIV.

PrEP Formulations

• Oral pills:
  • Truvada (TDF/FTC) – referred to as “TVA” in the lecture.
  • Descovy.
• Injection:
  • Apretude (cabotegravir injection).

PrEP Medications and Indications

Effectiveness of PrEP

• When taken as prescribed:
  • Reduces HIV risk from sex by about 99%.
  • Reduces HIV risk from injection drug use by at least 74% (pills).
• PrEP injections:
  • Not currently recommended for people who inject drugs.

Determining If PrEP Is Appropriate

Discuss risk factors using targeted questions:

Sexual risk:

• Have you had anal or vaginal sex in the past 6 months?
• Do you have a partner with HIV?
• Do you rarely or inconsistently use condoms?
• Have you been diagnosed with an STD in the past 6 months?

Injection drug risk:

• Do you inject drugs?
• Does your partner inject drugs and have HIV?
• Do you share needles or other injection equipment?

Postexposure prophylaxis (PEP) history:

• Have you ever been prescribed PEP?
• Are you continuing high-risk behaviors after PEP?
• Have you used multiple courses of PEP?
  • In such cases, PrEP is a better ongoing prevention strategy.

Special Populations and PrEP

• Pregnancy and breastfeeding:
  • PrEP may be considered to reduce risk of transmitting HIV to the baby while trying to conceive, during pregnancy, and while breastfeeding.
• Adolescents:
  • PrEP is approved for adolescents ≥ 77 lb who are at substantial risk.

Lyme Disease

Cause and Vector

• Etiology:
  • Borrelia burgdorferi, a spirochete bacterium.
• Vector:
  • Transmitted by the deer tick.
• System involvement:
  • Can affect musculoskeletal, cardiac, and nervous systems depending on disease stage.

Classic Skin Manifestation

• Erythema migrans:
  • “Bull’s-eye” rash.
  • Occurs in ~80–90% of patients with Lyme disease.
  • Usually appears at the site of the tick bite.

Stages of Lyme Disease

Diagnostic Testing for Lyme Disease

Two-Step Testing Strategy

1. Initial test:
   • Enzyme immunoassay (EIA) / ELISA.
   • If negative:
     • Consider alternate diagnoses.
     • If symptoms persist and suspicion remains high, consider retesting within 30 days.
2. If ELISA positive or equivocal:
   • Order Western blot:
     • IgM and IgG Western blot if symptoms < 30 days:
       • IgM (“M for miserable”) suggests acute or recent infection.
     • IgG only if symptoms ≥ 30 days:
       • IgM may no longer be present.
       • IgG indicates evidence of previous or ongoing infection.

Lyme Disease Prophylaxis After Tick Bite

Routine antibiotic prophylaxis after any tick bite is not recommended.

• Prophylactic single-dose doxycycline 200 mg can be considered only if all of the following are met:

  1. Tick was attached > 36 hours.
  2. Prophylaxis can be started within 3 days of tick removal.
  3. Local data indicate tick infection rate > 20%.
  4. Doxycycline is not contraindicated (e.g., not pregnant, no allergy).

• In practice, it is uncommon to meet all four criteria.

Treatment of Lyme Disease

• Indications for standard early treatment:
  • Early localized or early disseminated disease without neurologic or cardiac manifestations.
• First-line oral regimens:
  • Doxycycline.
  • Amoxicillin.
  • Cefuroxime.
• Second-line options:
  • Macrolides (for patients who cannot tolerate first-line agents).

Rocky Mountain Spotted Fever (RMSF)

Key Facts

• Tick-borne illness caused by a rickettsial organism (organism not named in transcript).
• Transmission:
  • Tick must be attached and feeding for 6–10 hours.

Classic Clinical Triad

• Fever.

• Severe headache.

• Rash.

• Rash:

  • Occurs in about 88–90% of cases.
  • Is a major diagnostic sign.
  • Appearance can vary; not every rash looks the same.

Clinical Importance

• RMSF is rapidly progressive and potentially fatal.
• Death can occur quickly if not treated promptly.

Diagnosis and Testing

• Serologic testing:
  • Used to confirm diagnosis, especially in the convalescent stage.
  • Not helpful for immediate decision-making due to delay in antibody development.

Management

• Do not wait for lab confirmation if clinical suspicion is high.
• Any patient with fever and rash:
  • Consider hospitalization.
  • Start doxycycline empirically.
  • “Err on the side of caution” and treat as RMSF until proven otherwise.
• Potential complications if untreated:
  • Amputations (from severe vascular compromise).
  • Hearing loss.
  • Paralysis.
  • Mental disability.

Influenza

Etiology and Epidemiology

• Caused by:
  • Influenza virus type A or B.
• Seasonal pattern:
  • In temperate climates, more common during winter months.
• Transmission:
  • Highly contagious.
  • Spread via respiratory secretions (coughing, sneezing).
• Viral shedding:
  • Virus can be shed for up to 24 hours before symptoms appear.
  • Contributes to rapid spread in communities.

Clinical Presentation of Influenza

Symptoms

• Abrupt onset of illness.
• Systemic:
  • High fever.
  • Chills.
  • Headache.
• Respiratory:
  • Dry cough.
  • Nasal congestion.
  • Sore throat.

Course of Illness

• Fever:
  • Often declines within 2–3 days, but can persist 4–8 days.
• Convalescent period:
  • Lasts 1–2 weeks.
  • Ongoing cough.
  • Marked malaise and fatigue.
  • Patients may feel like they “never quite get over it” for a while.

Physical Examination Findings

• Flushed face.
• Watery, irritated eyes.
• Skin:
  • Hot if febrile.
• Nasal passages:
  • Inflamed, with discharge.
• Lymph nodes:
  • May have mild lymphadenopathy.
• Throat:
  • Classically, no marked redness or exudates on the posterior pharynx (helps distinguish from streptococcal pharyngitis).

Diagnosis of Influenza

Specimen Collection

• Nasopharyngeal specimen is preferred.
• Best collected within 12–36 hours of symptom onset for optimal yield.

Testing Methods

• Gold standards:
  • Viral culture.
  • Reverse transcriptase polymerase chain reaction (RT-PCR) assay.
  • These are highly sensitive but results take several days, so rarely used for routine clinical decisions.
• Rapid influenza tests:
  • Commonly used in outpatient settings.
  • Provide faster results.
  • Less sensitive → risk of false negatives.

Management of Influenza

Identify High-Risk Patients

High risk for complications includes:

• Pregnant individuals.
• Very young children.
• Older adults.
• Immunosuppressed patients:
  • HIV infection.
  • Chronic systemic steroid use.
  • Other immunosuppressive medications (e.g., for autoimmune disorders).
  • Post–organ transplant patients.

These patients may require:

• Specialist referral.
• Consideration for hospitalization.

Indications for Urgent/Emergent Evaluation

• Rapid worsening of respiratory symptoms:
  • Increased shortness of breath, hypoxia.
• Signs of volume depletion:
  • Poor oral intake, dizziness, hypotension.

Such patients should be considered for ED evaluation and possible admission.

General Symptomatic Management

• Stay home from work or school while febrile.
• Supportive care:
  • Rest.
  • Adequate fluid intake.
  • Antipyretics (e.g., acetaminophen, ibuprofen).
  • Over-the-counter cold medications as needed.

Antiviral Treatment for Influenza

• There are four FDA-approved antiviral medications for influenza (names not specified in lecture).
• Key points:
  • Antivirals do not cure the flu.
  • They may:
    • Reduce symptom severity.
    • Shorten illness duration by roughly 1–2 days.
• Timing:
  • Most effective when started within 48 hours of initial fever/symptom onset.
• Indications:
  • Primarily recommended for high-risk patients.
  • Not routinely necessary for otherwise healthy individuals, although commonly prescribed in practice.

Influenza Vaccination

General Recommendations

• Annual flu vaccination is recommended for all persons ≥ 6 months of age.
• Especially important in:
  • Pregnant patients.
  • Very young children.
  • Older adults.
  • Immunocompromised persons (any cause).

Pediatric Consideration

• For children receiving the flu vaccine for the first time:
  • They should receive two doses, 4 weeks apart, to enhance immune response.

Types of Influenza Vaccines

• Live attenuated vaccine:
  • Can cause upper respiratory irritation:
    • Nasal congestion.
    • Runny nose.
    • Sore throat.
  • Does not cause true influenza.
  • Not currently recommended due to lower efficacy, but important to know criteria in case it returns to common use.

Tuberculosis (TB)

Transmission and Risk Populations

• Transmission:
  • Airborne—spread via respiratory droplets (e.g., coughing).
• High-risk groups:
  • Homeless individuals.
  • Malnourished individuals.
  • Those living in overcrowded housing.
  • Incarcerated persons.
  • Immunocompromised patients (including HIV).
  • Older adults.
  • People who abuse drugs.

Sites of Infection

• Primary site:
  • Lungs (~85% of TB cases).
• Extrapulmonary sites:
  • Kidneys.
  • Brain.
  • Bone.

Clinical Features of TB

Latent TB Infection (LTBI)

• No active disease.
• Asymptomatic.
• Organisms present but contained by immune system.

Active Pulmonary TB

• Symptoms:
  • Weight loss.
  • Night sweats.
  • Fatigue.
  • Cough (may be chronic).
  • Hemoptysis (coughing up blood) possible.
  • Fever.
• Physical exam findings:
  • Rales, especially in upper chest.
  • Lymphadenopathy.
  • Evidence of weight loss and fever.

Tuberculin Skin Test (TST / Mantoux Test)

Basics

• Measures delayed-type hypersensitivity to TB antigens.
• Becomes reactive 2–8 weeks after initial TB infection.

How to Read the Test

• Measure:
  • Induration (firm, raised area), not erythema (redness).
• Timing:
  • Read at 48–72 hours after intradermal placement.

Preferred Population for TST

• Children < 5 years:
  • TST is the preferred method of TB screening.

TST Positivity Criteria

Interpretation depends on the size of induration and patient risk factors:

Key principle:
The higher the risk, the smaller the induration needed to consider the test positive.

Limitations of the TST

Causes of False Positives

• Infection with non-tuberculous mycobacteria.
• Prior BCG vaccination:
  • Common in countries with high TB prevalence.
  • Can cause a positive TST even in the absence of TB disease.
• Technical errors:
  • Improper test administration.
  • Incorrect reading technique.
  • Use of the wrong antigen.

Causes of False Negatives

• Cutaneous anergy:
  • Severe immunosuppression (e.g., advanced HIV, certain cancers, medications).
  • Older age with poor immune function.
• Very recent TB infection:
  • Immune system has not yet mounted a detectable response.
• Very remote (old) TB infection.
• Very young age (immature immune system).
• Recent live virus vaccination.
• Overwhelming active TB disease.
• Concurrent viral illness.
• User or interpretation errors.

Interferon-Gamma Release Assays (IGRAs)

Blood-Based TB Tests

• Examples (trade names):
  • QuantiFERON-TB Gold.
  • T-Spot TB.
• These are serum blood draws that measure interferon-gamma release in response to TB antigens.

When IGRAs Are Preferred

• Individuals who have received BCG vaccination:
  • Less cross-reactivity compared with TST.
• People who are unlikely to return for TST reading:
  • Avoids the need for a 48–72 hour follow-up visit.

Interpretation

• Positive IGRA or TST:
  • Indicates infection with TB bacteria.
  • Further evaluation needed to determine:
    • Latent TB vs. active TB disease.
• Negative IGRA or TST:
  • Makes latent or active TB infection unlikely, though not impossible in all clinical contexts.

Next Steps After a Positive Screening Test

• Obtain a chest X-ray to:
  • Evaluate for evidence of active pulmonary TB.
  • Distinguish latent TB infection from active disease.

TB Treatment (Overview)

Note: Detailed management is typically coordinated by infectious disease specialists or public health TB clinics.

Latent TB Infection

• Definition:
  • Positive TST or IGRA.
  • Negative chest X-ray.
  • No clinical suspicion of active TB disease.
• Typical treatment:
  • Isoniazid (INH) and/or rifampin (referred to as “rifampen” in the lecture).

Active TB Disease

• Requires prolonged multi-drug therapy (about 6–9 months).
• Consists of:
  • Initiation phase.
  • Continuation phase.
• There are 10 FDA-approved TB drugs.
• Key first-line agents (as listed in lecture):
  • Isoniazid (INH).
  • Rifampin (RIF).
  • Pyrazinamide (PZA).
  • (A fourth first-line drug exists but was not named in the transcript.)
• Therapy is complex and must be tailored and supervised closely.

Key Terms & Definitions

• HIV (Human Immunodeficiency Virus):
  • Retrovirus that infects CD4 T cells and leads to progressive immune deficiency.
• AIDS (Acquired Immunodeficiency Syndrome):
  • Advanced HIV infection defined by CD4 < 200 cells/mm³ or HIV with specific opportunistic conditions.
• CD4 T cells:
  • Immune cells targeted by HIV; central to adaptive immunity.
• Window period:
  • Interval after HIV infection when virus is present but standard antibody tests remain negative.
• Seroconversion:
  • Development of detectable antibodies after infection.
• PrEP (Pre-exposure prophylaxis):
  • Daily or intermittent medication strategy to prevent HIV in high-risk persons.
• Erythema migrans:
  • Typical expanding, “bull’s-eye” rash of early Lyme disease.
• Bell’s palsy:
  • Acute facial nerve paralysis that can occur as a neurologic manifestation of Lyme disease.
• Rocky Mountain spotted fever (RMSF):
  • Acute tick-borne disease characterized by the triad of fever, severe headache, and rash; quickly fatal without treatment.
• Convalescent period:
  • Recovery phase after acute infection when symptoms gradually resolve but fatigue and residual complaints may persist.
• Tuberculin skin test (TST / Mantoux test):
  • Intradermal test that measures immune response to TB antigens via induration.
• Induration:
  • Hardened, raised area at a test site; used to interpret TST results.
• BCG vaccine (Bacillus Calmette–Guérin):
  • TB vaccine used in high-prevalence regions; can cause a positive TST result.
• Cutaneous anergy:
  • Inability to mount a skin test response due to impaired immunity.
• Interferon-gamma release assay (IGRA):
  • Blood test (e.g., QuantiFERON-TB Gold, T-Spot TB) measuring interferon-gamma response to TB antigens.

Summary and Study Priorities

Big-Picture Takeaways

• HIV/AIDS:
  • Understand the definition of AIDS, the significance of CD4 counts, and routine vs. high-risk screening.
  • Know the role of PrEP and differences between Truvada, Descovy, and Apretude.
• Lyme Disease:
  • Recognize erythema migrans and the three stages.
  • Memorize the two-step testing (ELISA → Western blot) and when to use IgM vs. IgG.
• Rocky Mountain Spotted Fever:
  • Remember the triad: fever, severe headache, rash.
  • Treatment with doxycycline should not be delayed for lab confirmation.
• Influenza:
  • Identify characteristic presentation and course.
  • Understand rapid testing limitations.
  • Know high-risk groups for complications and key vaccine types and indications.
• Tuberculosis:
  • Be able to interpret TST results using 5 mm / 10 mm / 15 mm cutoffs.
  • Distinguish between latent TB and active disease.
  • Recognize indications for IGRAs and basic first-line TB drugs.

Areas to Review Further

• Precise opportunistic infections and malignancies included in AIDS-defining criteria (beyond those listed).
• Detailed dosing regimens and durations for:
  • PrEP medications.
  • Lyme disease antibiotics.
  • TB treatment protocols (including the unnamed fourth first-line agent).
• Specific names and classes of the four approved influenza antivirals and their indications.
• Updated CDC HIV testing algorithm and any changes since 2014.
• Detailed RMSF causative organism and characteristic rash distribution patterns.

Focus your study on recognizing clinical patterns, knowing when to screen and treat aggressively, and understanding high-yield thresholds and algorithms (CD4 levels, TST cutoffs, Lyme testing stages, and indications for PrEP and antivirals).