Vector-Borne and Zoonotic Diseases

Tick-borne (spring–summer, nymphal feeding)

• Spirochetes: Borrelia burgdorferi (Lyme) via Ixodes scapularis/pacificus; reservoir is the white-footed mouse, with deer required only to sustain the adult tick. Transmission generally requires prolonged attachment (roughly 36+ hours), which is why prompt tick removal is protective (IDSA/AAN/ACR 2020 Lyme guideline).
• Obligate intracellular bacteria: Rickettsia rickettsii (RMSF) via Dermacentor spp. and, in the Southwest, the brown dog tick; Ehrlichia and Anaplasma via Amblyomma and Ixodes. These invade endothelium or leukocytes rather than remaining extracellular.
• Protozoa: Babesia microti shares the Ixodes vector, so Lyme co-infection is common and can also be transfusion-transmitted.

Mosquito-borne

• Plasmodium spp.: Anopheles bite at dusk/dawn; P. falciparum drives severe disease, P. vivax/ovale form hypnozoites causing relapse.
• Flaviviruses/alphaviruses: dengue, Zika, chikungunya via day-biting Aedes aegypti/albopictus; West Nile via Culex with a bird reservoir.

• Vector-mediated transmission and amplification: Arthropod vectors (mosquitoes, ticks, sandflies, blackflies) serve as biological hosts where the pathogen replicates or develops before transmission. The vector takes a blood meal, injecting saliva containing infectious organisms (sporozoites, merozoites, or bacteria) directly into the human bloodstream. This allows pathogens to bypass mucosal barriers and establish infection in target organs.

• Systemic inflammatory response and vascular dysfunction: Initial infection triggers innate immune responses with release of cytokines (TNF-α, IL-6, IL-1β) causing endothelial activation, increased vascular permeability, and plasma leakage. In severe disease (dengue hemorrhagic fever, malaria), this leads to hypovolemic shock, disseminated intravascular coagulation (DIC), and multi-organ failure from direct endothelial damage and thrombocytopenia.

• Parasite-specific pathogenic mechanisms:
• Malaria: Plasmodium parasites invade RBCs, causing hemolysis, sequestration of infected cells in microvasculature (cerebral malaria), and metabolic acidosis
• Trypanosomiasis: Trypanosomes evade immunity through antigenic variation and cause myocarditis, meningoencephalitis, and cardiomyopathy
• Leishmaniasis: Intracellular amastigotes survive in macrophages; visceral disease involves reticuloendothelial system infiltration

• Neurological invasion and immune-mediated damage: Many vector-borne pathogens cross the blood-brain barrier (West Nile virus, tick-borne encephalitis, African trypanosomiasis), causing aseptic meningitis or encephalitis through direct viral replication and/or immune-mediated inflammation with demyelination.

• Chronic sequelae from persistent infection or immunity: Some infections establish chronic parasitemia (Chagas disease, African sleeping sickness) or trigger chronic inflammatory responses leading to organ damage (cardiomyopathy, megacolon) even after pathogen clearance.

• Fever with myalgias, arthralgias, and headache: The classic prodrome of most vector-borne diseases (dengue, chikungunya, Lyme disease) presents as an acute febrile illness. Dengue characteristically causes severe retroorbital pain, while chikungunya causes debilitating joint pain that may persist for months. Lyme disease may present with milder systemic symptoms initially.

• Rash patterns as diagnostic clues: Dengue presents with a centripetal maculopapular rash appearing on days 3-7 (often sparing palms/soles); Rocky Mountain spotted fever shows a petechial rash starting on wrists/ankles spreading centrally; chikungunya causes a transient maculopapular rash; secondary syphilis (which can be acquired through contact) resembles other rashes but involves palms/soles involvement.

• Neurological manifestations: West Nile virus and tick-borne encephalitis present with meningitis or encephalitis (fever, headache, confusion, seizures, flaccid paralysis from anterior horn cell involvement). African sleeping sickness progresses through a hemolymphatic stage (fever, lymphadenopathy) to meningoencephalitis with sleep disturbances ("sleeping sickness").

• Gastrointestinal and hemorrhagic features: Dengue fever progresses through a critical phase (days 3-7) with severe abdominal pain, persistent vomiting, and hepatomegaly. Severe dengue hemorrhagic fever presents with mucosal bleeding, petechiae, and shock. Yellow fever causes hepatocellular necrosis with jaundice, abdominal pain, and hemorrhage (vomiting blood).

• Organomegaly and hematologic changes: Visceral leishmaniasis presents with hepatosplenomegaly, pancytopenia, and fever (undulant or continuous pattern) in immunocompromised patients; malaria causes splenomegaly and hemolytic anemia; African trypanosomiasis causes cervical lymphadenopathy (Winterbottom's sign).

• Cardiac manifestations: Chagas disease causes dilated cardiomyopathy with arrhythmias in chronic phase; myocarditis appears in yellow fever and dengue severe disease; Lyme disease presents with atrioventricular block and myopericarditis in early disseminated disease.

• Important variants by immunocompetence: Immunocompromised patients (HIV with CD4 <200, transplant recipients) with vector-borne diseases often present with higher parasitemia, more severe disease, and atypical presentations (e.g., severe skin manifestations in leishmaniasis, rapid progression in African sleeping sickness).

• Serological testing (ELISA, rapid tests): Most vector-borne diseases rely on antibody detection via IgM (acute) and IgG (past/chronic infection). Dengue uses NS1 antigen detection in first 5 days plus IgM/IgG. Lyme disease uses two-tier testing (ELISA followed by Western blot for confirmation due to high false-positive rate). Cross-reactivity between related viruses (dengue serotypes, flaviviruses) requires careful interpretation.

• Parasitological detection and microscopy: Malaria diagnosis requires thick and thin blood smears (gold standard) showing RBC parasitemia and allowing species identification and quantification; visceral leishmaniasis uses bone marrow or splenic aspiration showing amastigotes; trypanosomiasis uses blood smears (hemolymphatic stage) and CSF examination (meningoencephalitis stage); filariasis uses nocturnal blood smears correlating with vector feeding time.

• Nucleic acid amplification (PCR/RT-PCR): High sensitivity and specificity during acute viremia window (first 7-10 days). Essential for West Nile virus and tick-borne encephalitis diagnosis, especially in CSF. RT-PCR confirms dengue, chikungunya, and Zika in early infection. Culture is rarely used clinically due to BSL-3/4 requirements.

• Tissue and fluid sampling: Bone marrow aspiration or splenic puncture shows amastigotes in leishmaniasis (more sensitive than blood in visceral disease). Lumbar puncture with CSF analysis (pleocytosis with lymphocytic predominance, protein elevation, normal glucose) confirms CNS involvement in meningitis/encephalitis. Skin biopsy shows granulomas in cutaneous leishmaniasis.

• Imaging and clinical correlates: Brain MRI shows hyperintense lesions in tick-borne encephalitis (thalamus, brainstem) and West Nile encephalitis. Chest X-ray may show pneumonitis in severe dengue or yellow fever. EKG detects AV block in Lyme carditis and arrhythmias in Chagas disease.

• Important diagnostic timing: Early in infection, antigen/nucleic acid testing is more sensitive than antibodies. Timing relative to symptom onset affects test selection (e.g., malaria smears should be repeated if initial negative but suspicion remains high). Serology may be falsely negative early or falsely positive from previous exposure/vaccination.

• Antimalarial therapy (species-dependent):
• Plasmodium falciparum/vivax (non-severe, no complications): Artemether-lumefantrine (Coartem) or artemisinin derivatives (faster parasite clearance than older drugs). Alternative: atovaquone-proguanil (Malarone) or quinine + doxycycline
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Disease complications — emergencies flagged

• Cerebral malaria (EMERGENCY): cytoadherence of *P. falciparum*–infected RBCs to cerebral microvascular endothelium causes sequestration and coma; signal is impaired consciousness or seizure with parasitemia, plus hypoglycemia and lactic acidosis. Severe malaria also brings ARDS, acute kidney injury, and blackwater fever (massive intravascular hemolysis with hemoglobinuria). CDC guidance is IV artesunate without waiting for species confirmation.
• Severe dengue (EMERGENCY): cytokine-driven endothelial permeability produces plasma leakage at defervescence; signals are a rising hematocrit with falling platelets, ascites/pleural effusion, and narrow pulse pressure. WHO warning signs — persistent vomiting, mucosal bleeding, severe abdominal pain, lethargy — mandate admission and crystalloid resuscitation.
• Fulminant RMSF (EMERGENCY): rickettsial endothelial invasion causes vasculitis with capillary leak, noncardiogenic pulmonary edema, cerebral edema, and gangrene; hyponatremia, thrombocytopenia, and transaminitis with a spreading petechial rash are the tell. Mortality rises sharply after roughly day 5 of illness untreated.
• Lyme carditis (EMERGENCY): spirochetal invasion of the AV node produces variable, often high-grade AV block; a young patient with syncope and marked PR prolongation needs telemetry, IV ceftriaxone, and temporary pacing if unstable — permanent pacemakers are usually unnecessary because block resolves.
• Chronic sequelae: Lyme arthritis (large joints, knee), post-infectious neuropathy, and babesiosis-related hemolysis with DIC in asplenics.

Treatment complications

• Jarisch–Herxheimer reaction: lysis of spirochetes releases lipoproteins causing fever, rigors, and hypotension within hours of the first antibiotic dose; supportive care, not drug discontinuation.
• Doxycycline: photosensitivity and pill esophagitis; dental staining fears are not a reason to withhold it for suspected rickettsial disease in young children (AAP Red Book/CDC).
• Primaquine/tafenoquine: oxidative hemolysis in G6PD deficiency — quantitative G6PD testing before radical cure is mandatory.
• Artesunate: delayed post-artemisinin hemolysis weeks later; check a follow-up hemoglobin.
• Prolonged/IV antibiotics for persistent post-treatment Lyme symptoms: no benefit and risk of line sepsis (IDSA/AAN/ACR).

• Treat rickettsial disease on suspicion, never on serology: doxycycline is first-line for RMSF, ehrlichiosis, and anaplasmosis in all ages, including children under 8 (CDC MMWR 2016; AAP Red Book). The single best next step in a febrile patient with tick exposure and a wrist/ankle petechial rash is empiric doxycycline. Common distractors: waiting for confirmatory titers, chloramphenicol, or a sulfonamide — sulfa drugs worsen RMSF.
• Rash direction is the discriminator: RMSF spreads centripetally from wrists/ankles inward and involves palms/soles; early RMSF may be spotless. Contrast with the centrifugal, palm-sparing rash of dengue.
• Erythema migrans is a clinical diagnosis: per the IDSA/AAN/ACR 2020 guideline, treat with oral doxycycline (or amoxicillin/cefuroxime in pregnancy or young children) and do not order two-tier serology — it is frequently negative in the first weeks.
• Tick-bite prophylaxis: a single 200 mg dose of doxycycline within 72 hours of removal of an engorged Ixodes tick in a high-incidence area.
• Malaria workup: thick and thin smears, repeated every 12–24 hours before excluding disease. Severe falciparum (impaired consciousness, high parasitemia, acidosis) → IV artesunate (CDC). Check quantitative G6PD before primaquine or tafenoquine for the hypnozoite radical cure of vivax/ovale.
• Dengue deteriorates as the fever breaks: severe disease follows a secondary infection with a heterologous serotype via antibody-dependent enhancement. Give isotonic fluids and avoid NSAIDs and aspirin (bleeding risk, Reye syndrome).
• Babesiosis: Maltese cross tetrads and ring forms without pigment on smear, hemolytic anemia, and severe disease in asplenics; treat with atovaquone plus azithromycin and screen for concurrent Lyme, since both ride Ixodes.
• Persistent fatigue after documented, adequately treated Lyme is not active infection — prolonged antibiotics are not indicated.