Microbial Systemic Diseases and Immune Interactions (Chapter 21): Measles, Lyme Disease, Mononucleosis, and Malaria

Microbial Systemic Disease and Immune Interactions

Overview

This chapter explores major microbial diseases affecting the cardiovascular and systemic systems, focusing on their causative agents, pathogenesis, immune interactions, epidemiology, diagnosis, treatment, and prevention. The diseases covered include Measles, Lyme Disease, Infectious Mononucleosis, and Malaria.

Cardiovascular System: Defenses and Vulnerabilities

System Structure and Defense Mechanisms

• Closed System: The cardiovascular system is a closed network of the heart and blood vessels, normally free of microbes (axenic).

• Mechanical Defenses: Blood is protected from infection by physical barriers and immune surveillance.

• Routes of Infection: Microbes can enter through skin breaks and spread via blood and lymph.

Measles (Rubeola)

Etiology and Transmission

• Pathogen: Measles virus (a paramyxovirus).

• Transmission: Highly contagious; spreads via droplet and airborne transmission when an infected person coughs or sneezes.

• Infectivity: Virus remains infectious in the air for up to 2 hours. One infected person can spread the virus to 12–18 others.

Pathogenesis

• Begins as a respiratory infection, then spreads through blood and lymph.

• Active Tc cells kill infected cells, causing most symptoms.

• Recovery takes 2–3 weeks; 1–5% of infected children may die.

• Immune Amnesia: Measles infection erases preexisting immune memory, increasing vulnerability to secondary infections for 2–3 years post-infection.

Clinical Manifestations

• Incubation Period: 8–12 days post-exposure; contagious 4 days before symptoms start.

• Early (Prodromal) Symptoms: Fever, sore throat, headache, dry cough, conjunctivitis.

• Koplik's Spots: Small white lesions in the mouth, pathognomonic for measles.

• Late Symptoms: Full-body rash appears.

Epidemiology

• Humans are the only natural host; candidate for eradication.

• Highly contagious; 90% of non-immune contacts develop disease.

• Requires dense populations of susceptible individuals for sustained transmission.

• Patients are infectious from onset of prodromal symptoms until 2–4 days after rash development.

• Still causes over 100,000 deaths annually, mostly in children under 5.

Diagnosis and Treatment

• Diagnosis: Clinical signs (especially Koplik's spots); serological testing for measles antigen.

• Treatment: Supportive therapy, vitamin A, antibodies against measles virus, ribavirin.

Prevention

• Vaccine: Live, attenuated vaccine (part of MMR) given at ~12 months and ~4 years.

• Elimination requires two-dose coverage of at least 90–95% of the population.

• Post-exposure prophylaxis: Vaccine within 72 hours or passive immunization with immunoglobulin within 6 days for those who cannot be vaccinated.

Lyme Disease

Pathogen and Virulence Factors

• Pathogen: Borrelia burgdorferi (Gram-negative spirochete).

• Burrows into tissues; lacks iron-containing enzymes and molecules.

• Changes outer surface proteins (OSPs) for antigenic variation, evading immune detection.

Transmission and Life Cycle

• Vector: Hard ticks of the genus Ixodes.

• Reservoir: White-footed mouse; nymphs and adults transmit to large animal hosts.

• Ticks must feed for 36–48 hours to transmit enough spirochetes for infection.

• Organisms spread via blood and lymph, can accumulate in joints, and remain dormant.

Clinical Stages and Symptoms

• Stage 1 (Early Localized): 3–30 days post-bite; expanding red rash (erythema migrans), flu-like symptoms.

• Stage 2 (Early Disseminated): Days to months post-bite; multiple rashes, arthritis, cardiac (arrhythmia, myocarditis), neurologic (Bell's palsy, meningitis) symptoms.

• Stage 3 (PTLDS/Chronic Lyme): Weeks to years later; severe fatigue, sleep impairment, joint pain, depression, headaches.

Epidemiology

• Discovered in 1975 (Lyme, Connecticut).

• One of the most reported vector-borne diseases in the U.S.; ~476,000 new cases annually.

• Incidence increased due to human encroachment into woodland areas and ecological changes.

Diagnosis

• Based on clinical signs, exposure history, and presence of antibodies against Borrelia.

• Negative antibody test does not rule out disease (may be too early, immune suppression, or strain not detected).

Treatment

• Early phase: Doxycycline, amoxicillin, or cefuroxime axetil (14–28 days); IV drugs for severe cases.

• Late phase: Difficult to treat; symptoms often immune-mediated.

Prevention

• Protective clothing, tick repellents (DEET), prompt tick removal.

• Vaccine development ongoing (VLA15 in clinical trials).

Infectious Mononucleosis (Epstein-Barr Virus, EBV)

Pathogen and Virulence Factors

• Pathogen: Epstein-Barr virus (EBV), Human herpesvirus 4 (HHV-4), enveloped dsDNA virus.

• Becomes latent in B lymphocytes, causing lifelong infection.

• May contribute to certain cancers and chronic fatigue syndrome.

Pathogenesis

• Transmitted via saliva ("kissing disease"), coughing, sneezing, or sharing utensils.

• Infects epithelial cells of throat and salivary glands, then B lymphocytes (viremia).

• Cytotoxic T lymphocytes (CTLs) kill infected B cells, causing symptoms.

Clinical Manifestations

• Incubation: 4–6 weeks.

• Initial: Severe sore throat, fever, weakness.

• Later: Swollen lymph nodes, enlarged spleen, extreme fatigue, nausea, headache, rash.

• Symptoms resolve in 1–2 months; fatigue may persist for months.

• In children <6, illness is mild and resembles common respiratory infections.

Epidemiology

• 95% of adults worldwide have been infected.

• Peak incidence in U.S.: ages 15–24.

• Infection in childhood is milder, more severe in adolescents/adults.

Diagnosis and Treatment

• Diagnosis: Presence of large, lobed B lymphocytes with atypical nuclei; antibody tests for EBV antigens.

• Treatment: Supportive care; avoid contact sports to prevent splenic rupture.

Prevention

• No vaccine available.

• Prevention is difficult due to persistent viral shedding in saliva.

Malaria

Pathogen and Virulence Factors

• Pathogen: Protozoa of the genus Plasmodium (at least 5 species infect humans).

• Virulence factors: Reproductive cycle in RBCs (no MHC), antigenic variation, adhesins, host biochemical manipulation.

Life Cycle and Pathogenesis

• Transmitted by Anopheles mosquitoes.

• Life cycle stages: Sporozoite (mosquito to human), liver stage, erythrocytic cycle (RBC infection), gametocyte stage (back to mosquito).

• Ring stage in RBCs is diagnostic; synchronous lysis of RBCs every 48–72 hours causes cyclic fevers.

Clinical Manifestations

• Asymptomatic: Parasites present, no symptoms.

• Uncomplicated: Fever, chills, sweating, headache, nausea, vomiting, diarrhea, anemia.

• Severe (usually P. falciparum): Organ dysfunction, coma, pulmonary and renal complications.

• Loss of RBCs leads to anemia, jaundice, and fatigue.

Genetic Resistance

• Large structural variants in glycophorin genes are protective.

• Sickle cell trait (heterozygous HbS), hemoglobin C, G6PD deficiency, and lack of Duffy antigen confer resistance to malaria.

Epidemiology

• Humans are the reservoir for human malaria.

• Endemic in 109 countries; 300–500 million cases and ~1.2 million deaths annually (mostly in sub-Saharan Africa).

• Transmission influenced by climate, vector presence, and human movement.

• ~1,700 cases/year in the U.S. (mostly imported).

Diagnosis and Treatment

• Diagnosis: Microscopy of blood smears (ring forms in RBCs), antibody detection, travel history.

• Treatment: Drug choice depends on resistance patterns; options include chloroquine, malarone, mefloquine, quinine, and antibiotics. Severe cases may require antipyretics and blood transfusions.

Prevention

• Limit mosquito contact: Insecticides, removal of standing water, protective clothing, DEET repellents, mosquito netting.

• Prophylactic drugs (e.g., malarone) for travelers.

• Vaccine development and genetically modified mosquitoes are under investigation.

Summary Table: Key Features of Systemic Microbial Diseases

Disease	Pathogen	Transmission	Key Symptoms	Diagnosis	Treatment	Prevention
Measles	Measles virus	Droplet/airborne	Fever, rash, Koplik's spots	Clinical, serology	Supportive, vitamin A	MMR vaccine
Lyme Disease	Borrelia burgdorferi	Tick bite (Ixodes)	Bull's-eye rash, arthritis, neuro/cardiac symptoms	Clinical, antibody test	Antibiotics (early)	Tick avoidance, vaccine (in development)
Mononucleosis	Epstein-Barr virus	Saliva	Sore throat, fatigue, lymphadenopathy	Clinical, atypical lymphocytes, serology	Supportive	None
Malaria	Plasmodium spp.	Mosquito (Anopheles)	Cyclic fever, anemia, jaundice	Blood smear, serology	Antimalarials	Vector control, prophylaxis

Additional info: This summary integrates and expands upon the provided lecture slides and notes, ensuring coverage of all major learning objectives and providing academic context for exam preparation.