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 pathogens, pathogenesis, immune interactions, epidemiology, diagnosis, treatment, and prevention. The diseases covered include Measles, Lyme Disease, Mononucleosis (Epstein-Barr Virus), and Malaria.

Cardiovascular System: Defenses and Vulnerabilities

System Structure and Defenses

• Closed System: The cardiovascular system is a closed network of blood vessels and the heart, minimizing exposure to external microbes.

• Mechanical Defenses: Includes physical barriers and immune surveillance.

• Axenic Blood: Blood is normally free of microbes; infections occur via skin breaks or systemic spread.

Measles (Rubeola)

Pathogen and Transmission

• Measles virus: Highly contagious, transmitted via droplet and airborne routes.

• Virus remains infectious in the air for up to 2 hours.

• Average infected person can spread the virus to 12–18 others.

Pathogenesis

• Initial infection in respiratory tract cells.

• Spreads systemically via blood and lymph.

• Active Tc cells (cytotoxic T cells) kill infected cells, causing most symptoms.

• Immune Amnesia: Loss of preexisting immune memory and difficulty establishing new memory, lasting 2–3 years post-infection.

Signs and Symptoms

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

• Early (Prodromal): Fever, sore throat, headache, dry cough, conjunctivitis, Koplik spots in the mouth.

• Late: Full body rash appears.

Epidemiology

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

• Highly contagious: 90% of non-vaccinated exposed individuals develop disease.

• Requires 90–95% immunization coverage for herd immunity.

• Measles was previously eliminated in the US and Americas but is resurging due to reduced vaccination rates.

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

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

• Two-dose coverage of at least 90–95% required for elimination.

• Post-exposure: Vaccine within 72 hours, passive immunization with immunoglobulin within 6 days.

Lyme Disease

Pathogen and Virulence Factors

• Borrelia burgdorferi: Gram-negative spirochete.

• Burrows into tissues, lacks iron-containing enzymes.

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

Pathogenesis

• Vector: Hard ticks of genus Ixodes.

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

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

• Organisms spread via blood/lymph, accumulate in joints (arthritis), can remain dormant.

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).

• Stage 3 (PTLDS/Chronic): 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 US (~476,000 cases/year).

• Incidence increased due to ecological changes (deer, mouse, coyote populations).

Diagnosis

• Clinical signs and exposure history.

• Confirmed by antibodies against Borrelia (may take >4–6 weeks to develop).

Treatment

• Antimicrobial drugs: doxycycline, amoxicillin, cefuroxime axetil (14–28 days for early phase).

• IV drugs for neurological/cardiac forms.

• Later phase treatment is difficult due to immune-mediated symptoms.

Prevention

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

• Vaccine development ongoing (VLA15 multivalent subunit vaccine).

Mononucleosis (Epstein-Barr Virus, EBV)

Pathogen and Virulence Factors

• Epstein-Barr virus (EBV): Human herpesvirus 4 (HHV-4), enveloped, double-stranded DNA virus.

• Becomes latent in B lymphocytes, causing lifelong infection.

• May play a role in chronic fatigue syndrome, B cell lymphomas, oral hairy leukoplakia.

Pathogenesis

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

• Infects epithelial cells of throat and parotid glands, then B lymphocytes.

• Lytic replication releases virions into bloodstream (viremia).

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

Signs and Symptoms

• Appear 4–6 weeks after infection.

• Severe sore throat, fever, weakness, swollen lymph nodes, enlarged spleen, extreme fatigue, nausea, headache, skin rash.

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

• In children

Epidemiology

• 95% of adults worldwide have been infected.

• Peak incidence in US: ages 15–24.

• Childhood infection less likely in areas with high hygiene standards.

Diagnosis

• Presence of large, lobed B lymphocytes with atypical nuclei and neutropenia.

• Serological tests for EBV antigens (VCA, EA, EBNA).

Treatment and Prevention

• Supportive care; most recover without treatment in 2–4 weeks.

• Avoid contact sports during recovery (risk of spleen rupture).

• No vaccine; prevention is difficult due to persistent virus in saliva.

Malaria

Pathogen and Virulence Factors

• Plasmodium species (protozoa); at least 5 species infect humans.

• Reproductive cycle occurs in red blood cells (no MHC presentation).

• Genetic and antigenic variation; adhesins for cell receptor binding.

• Alters host biochemistry, increasing mosquito attraction.

Life Cycle

• Sporogenic cycle: Occurs in mosquito vector.

• Erythrocytic cycle: Parasite invades RBCs, feeds on hemoglobin, reproduces, and lyses RBCs every 48–72 hours.

Pathogenesis and Symptoms

• Can be asymptomatic, uncomplicated, or severe.

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

• Severe: Organ dysfunction, coma, pulmonary/renal complications; most often caused by P. falciparum.

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

• Immunity develops gradually after survival of acute stages.

Genetic Traits Conferring Resistance

Genetic Trait	Protection Mechanism
Sickle cell trait (HbS)	Relatively protected from severe/uncomplicated malaria
Hemoglobin C	Protection against severe malaria (mechanism unclear)
G6PD deficiency	Protection against uncomplicated malaria (mechanism unknown)
Lack of Duffy antigen	Prevents infection by P. vivax

Epidemiology

• Humans are the reservoir for human malaria.

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

• Transmission affected by climate, movement of infected individuals/mosquitoes.

• ~1700 cases/year in US (mostly travelers/immigrants).

Diagnosis

• Microscopy of blood smears (ring forms in RBCs).

• Serological tests for antibodies against Plasmodium.

• Travel history is important for differential diagnosis.

Treatment

• Drug choices depend on resistance patterns: chloroquine, malarone, mefloquine, quinine, antibiotics with quinine.

• Severe cases may require antifever medication 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 under investigation.