Hematologic infections Notes

NOTES NOTES HEMATOLOGIC INFECTIONS GENERALLY, WHAT ARE THEY? PATHOLOGY & CAUSES Taxonomy ▪ Apicomplexan phylum protozoa → infectious hematological diseases Replication/multiplication ▪ Arthropod transmission Transmission ▪ Multiple life cycle stages (host-, vectordependent) DIAGNOSIS LAB RESULTS ▪ Blood smear: best intra-erythrocyte location diagnosis TREATMENT ▪ See individual infections SIGNS & SYMPTOMS ▪ See individual infections OSMOSIS.ORG 411

BABESIA osms.it/babesia PATHOLOGY & CAUSES RISK FACTORS ▪ Malaria-like parasitic infection ▫ Ixodes tick transmission ▪ Phylum Apicomplexa (same as Plasmodium, Toxoplasmosis) ▪ Common species ▫ Babesia microti most predominant (northeast, upper midwest United States) ▫ B. duncani (Western United States) ▫ B. divergens (Europe) ▪ Endemic area resident ▪ Endemic area travel, especially May– September ▪ Blood transfusion (last six months) ▪ Age > 50 ▪ Biologically male ▪ Asplenia ▪ Decreased immunity (malignancy, HIV/ AIDS infection, immunosuppressive drugs) ▪ Coinfection with Borrelia and/or Anaplasma ▪ Premature birth CAUSES COMPLICATIONS ▪ Ixodes scapularis tick: only recognized vector ▫ Same tick transmits Borrelia burgdorferi (→ Lyme disease; concurrently infects ⅔ babesiosis-infected individuals) and Anaplasma phagocytophilum (→ human granulocytic anaplasmosis; concurrently infects ⅓ babesiosis-infected individuals) ▫ Contaminated blood transfusion → rare human-to-human transmission ▪ Life cycle ▫ Two hosts: white-footed mouse, Ixodes tick (definitive) ▫ Blood meal → Babesia-infected tick sporozoites into mouse host → sporozoites directly invade mature mouse erythrocytes → sporogony (asexual reproduction; budding) → in blood, some parasites differentiate into male, female gametes → gametes unite → sporogonic cycle → sporozoites → tick bites human → 1–4 week incubation → sporozoites enter erythrocytes → sporogony ▪ Sporogony ▫ Asynchronous with host → no massive hemolysis (versus malaria) ▪ Tick’s nymph stage is most infectious 412 OSMOSIS.ORG ▪ ↑ occurence in anemic/parasitemic individuals ▫ Congestive heart failure ▫ Noncardiac pulmonary edema ▫ Acute respiratory distress syndrome ▫ Splenic infarct ▫ Splenic rupture ▫ Septic shock ▫ Myocardial infarction ▫ Disseminated intravascular coagulation ▫ Death SIGNS & SYMPTOMS ▪ Mostly asymptomatic, may persist undiagnosed months/years ▪ Blood-stage parasite multiplication → clinical manifestation ▪ Non-specific flu-like symptoms (misdiagnosis common) ▫ Fatigue (gradual onset) ▫ Fever, chills, sweats ▫ Headache, myalgia, arthralgia ▫ Anorexia, nausea ▫ Cough

Chapter 77 Hematologic Infections ▪ Severe manifestations include malaria-like illness (fever, fatigue, malaise) + hemolytic anemia manifestation ▪ B. microti case-fatality rate is 5% ▪ B. divergens infections case-fatality rate is 42% ▫ Disseminated intravascular coagulation, bleeding diathesis ▫ Acute renal failure ▫ Cardiopulmonary complications (e.g. hypotension, poor perfusion, pulmonary edema) OTHER INTERVENTIONS ▪ Severe disease (parasitemia > 4%) ▫ Antimicrobial + exchange transfusion Prevention ▪ Personal: avoid endemic areas; long pants, shirts minimize exposed skin ▪ Tick repellant on skin (e.g. DEET) ▪ Post-exposure tick checks ▪ No antibiotic prophylaxis DIAGNOSIS LAB RESULTS Blood smear ▪ Wright/Giemsa staining ▫ Thin: rapid, ↓ microscopy experience required ▫ Thick: ↑ accurate, ↑ microscopy experience required ▫ Pathognomic tetrad “Maltese cross” visible in erythrocyte Laboratory ▪ Thrombocytopenia ▪ Reticulocytosis ▪ ↓ Hematocrit ▪ ↓ Hemoglobin ▪ ↑ Lactate dehydrogenase ▪ ↓ Haptoglobin ▪ ↑ Liver function tests ▪ ↑ Creatinine Polymerase chain reaction (PCR) ▪ Speciation (useful for low-level parasitemia) Serology ▪ Immunofluorescent antibody testing; species specific TREATMENT ▪ Asymptomatic: no treatment MEDICATIONS ▪ Symptomatic disease: azithromycin + atovaquone OSMOSIS.ORG 413

PLASMODIUM SPECIES (MALARIA) osms.it/malaria PATHOLOGY & CAUSES ▪ Anopheles mosquito vector → parasitic hematologic infection ▪ Four major malarial parasite species ▫ Plasmodium falciparum: most lethal, most drug-resistant (sub-Saharan Africa) ▫ P. vivax: widest geographic distribution, relapsing species ▫ P. ovale: relapsing species (western areas of sub-Saharan Africa) ▫ P. malariae: AKA ‘benign’ malaria (mild course) ▪ P. knowlesi: normally infects macaques, recent cause of human malaria cases ▪ Erythrocytic life cycle stage ▫ In erythrocytes → parasites can undergo asexual schizogony/ sexual differentiation (necessary for transmission) → gametocytes ▪ Asexual schizogony ▫ Trophozoites (parasite name once inside erythrocyte) digest host cell hemoglobin (amino acids, energy source) → schizont → undergoes mitosis → differentiates into merozoites → erythrocyte rupture → merozoite bloodstream release → fever, malarial symptoms CAUSES ▪ Exoerythrocytic (sporogonic; blood) life cycle stage ▫ Blood-stage gametocytes in other host (e.g. human) → female Anopheles mosquito blood meal → mosquito multiplication, growth cycle → 10–18 day incubation → sporozoites in mosquito salivary gland → human bite → sporozoite inoculation → hematogenous translocation to liver → rapid hepatic parenchymal cell invasion → parasites undergo exoerythrocytic schizogony (asexual multiplication) → development, multiplication → 7–14 day incubation → merozoite development → invade erythrocytes → symptomatic stage develops → P. ovale, P. vivax can differentiate into quiescent stage → hypnozoite → can re-enter into schizogony → reemerge to invade erythrocytes ▫ Blood stage → malaria symptoms ▫ Mosquito vector does not have parasite presence 414 OSMOSIS.ORG Figure 77.1 A peripheral blood film taken from an individual with Plasmodium malariae infection. There is a mature schizont, composed of 6-12 merozoites, contained within a red blood cell. ▪ P. malariae ▫ Low-level persistence possible for decades without diagnosis, treatment ▪ P. vivax ▫ Prefers erythrocytes with Duffy blood group antigen (rare in persons from West and Central Africa); prefers reticulocytes but will also invade mature erythrocytes ▪ Others preferentially invade mature erythrocytes

Chapter 77 Hematologic Infections ▪ P. falciparum ▫ Develop ‘knobs’ on infected erythrocytes in late trophozoite stage → parasitized erythrocytes adhere to capillary endothelium → various organ sequestration (notably brain) → cerebral malaria ▪ Most malaria deaths ▫ Children < five years old in hightransmission areas COMPLICATIONS Coma Seizure Severe anemia Acute renal failure ▫ Acute tubular necrosis secondary to hypoperfusion, hypovolemia ▪ Acute respiratory distress syndrome ▪ Shock ▪ Septicemia ▪ ▪ ▪ ▪ SIGNS & SYMPTOMS RISK FACTORS ▪ Poor rural populations in endemic areas ▪ Proximity to standing water ▫ Larvae breeding site (e.g. agriculture, irrigation ditches) ▪ Travel in endemic areas ▪ Blood transfusion (last six months) ▪ Lack of insect repellant, chemoprophylaxis, personal protective measures (long pants, shirts, mosquito nets) ▪ Duffy blood group antigen-positive individuals Protective factors ▪ P. falciparum protection: sickle cell trait (heterozygotes) ▪ P. vivax: Duffy blood group antigennegative individuals ▪ Febrile paroxysm (hallmark feature) ▫ 10–12 hours of intense rigors, chills → high fever, profuse diaphoresis ▫ Febrile seizure potential ▪ Non-specific complaints ▫ Headache, malaise, myalgia, arthralgia ▪ Abdominal pain, diarrhea, vomiting ▪ Possibly remarkably asymptomatic between episodes ▪ P. falciparum cerebral effects ▫ Significant morbidity, mortality (delirium, confusion, seizures → declining mental status → coma → death) ▪ Parasitemia, cytokine disturbance → hypotension, metabolic acidosis, hypoglycemia ▪ Anemia (high parasitemia → more pronounced) ▪ Sequestration, red blood cell destruction by spleen → hypersplenism DIAGNOSIS LAB RESULTS Giemsa stain blood smear ▪ Thin: rapid, ↓ microscopy experience required ▪ Thick: ↑ accurate, ↑ microscopy experience required ▪ P. falciparum: red blood cells contain multiple parasites, ring forms, lack of schizonts ▪ Banana-shaped gametocyte form OSMOSIS.ORG 415

Rapid diagnostic test ▪ 15–20 minute results ▪ Histidine-rich protein 2: detects P. falciparum PCR ▪ Supportive laboratory results (nondiagnostic) ▫ Normocytic hemolytic anemia ▫ Thrombocytopenia TREATMENT MEDICATIONS ▪ Severe malaria ▫ Quinidine + doxycycline/tetracycline/ clindamycin/artesunate (test for G6PD deficiency) ▪ Uncomplicated malaria ▫ Chloroquine-sensitive strain: chloroquine phosphate/ hydroxychloroquine (blocks Plasmodium heme polymerase) ▫ Chloroquine-resistant strain: atovaquone-proguanil, mefloquine, artesunate, quinine-based regimens ▪ P. ovale, P. vivax: + primaquine for hypnozoite (test for G6PD deficiency) OTHER INTERVENTIONS Figure 77.2 A histological section of the placenta from an individual infected with malaria. The numerous black dots within the red blood cells are malaria organisms. 416 OSMOSIS.ORG Prevention ▪ Chemoprophylaxis ▪ Avoid outdoors (dusk/dawn) ▪ Reduce exposed skin (long pants, shirts) ▪ Bed netting/mosquito nets ▪ Insect repellent (DEET 30–50%)